ARC-HD: Alternatives for Reducing Chorea in Huntington Disease

• Sponsor: Auspex Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01897896
• Collaborator: (none)
• Enrollment: 119
• Locations: 38
• Arms: 2
• Actual Duration (Months): 45.3
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of SD-809 extended release (ER) in participants switching from tetrabenazine to SD-809 ER. In addition, the safety and tolerability of long-term treatment with SD-809 ER will be assessed in "Switch" participants as well as "Rollover" participants completing a randomized, double blind, placebo-controlled study of SD-809 ER.

Condition or Disease	Intervention/Treatment	Phase
Chorea Associated With Huntington Disease	Drug: SD-809	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Long Term Safety Study of SD-809 ER in Subjects With Chorea Associated With Huntington Disease
• Actual Study Start Date: Nov 12, 2013
• Actual Primary Completion Date: Aug 21, 2017
• Actual Study Completion Date: Aug 21, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rollover Cohort: SD-809 ER Participants who completed study SD-809-C-15 (NCT01795859, including 1-week washout period and Week 13 evaluation), will receive 6 milligrams (mg) SD-809 ER tablet once daily as a starting dose in this study. Dose titration will be continued through Week 8 to optimize dose. Dose of SD-809 ER can be adjusted weekly in increments of 6 milligrams per day (mg/day) (6 or 12 mg/day after a total daily dose of 48 mg is reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher will be administered twice daily. Maximum total daily dose of SD-809 ER will be 72 mg/day (36 mg twice daily), unless participant is receiving a strong CYP2D6 inhibitor(such as, paroxetine, buproprion, fluoxetine), in which case maximum total daily dose will be 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (further dose adjustments are permitted, if clinically indicated) will be continued until SD-809 ER become commercially available in United States.	Drug: SD-809; SD-809 tablets will be provided in dose strengths of 6, 9 and 12 mg.; Other Names: Deutetrabenazine
Experimental: Switch Cohort: SD-809 ER Participants who were receiving an approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, will be converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state area under the curve (AUC) of total (alpha+beta)- Dihydrotetrabenazine (HTBZ) metabolites that is predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants will remain on initial dose of SD-809 ER through Week 1. Dose adjustment will be continued through Week 4 to optimize the dose. Dose of SD-809 ER can be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg is reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments are permitted, if clinically indicated) will be continued until SD-809 ER become commercially available in United States.	Drug: SD-809; SD-809 tablets will be provided in dose strengths of 6, 9 and 12 mg.; Other Names: Deutetrabenazine

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Entire Treatment Period [Baseline to follow-up visit (up to approximately 3 years 9 months)]

   An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=inability to carry out usual activities. Drug-related TEAEs: TEAEs with possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

2. Rollover Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Titration [Day 1 to end of Week 8]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

3. Switch Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Dose Adjustment [Day 1 to end of Week 4]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

4. Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Long Term Stable Dose Treatment [Week 8 to follow-up visit (up to approximately 3 years 9 months)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Secondary Outcome Measures

1. Change From Baseline in Clinical Laboratory Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets) at Week 158 [Baseline, Week 158]

   Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Change from baseline in basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets cells at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed values at Week 158 were used to calculate the change from baseline value at Week 158.

2. Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes Mean Corpuscular Volume) at Week 158 [Baseline, Week 158]

   Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Change from baseline in erythrocytes mean corpuscular volume at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

3. Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes) at Week 158 [Baseline, Week 158]

   Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Change from baseline in erythrocytes at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

4. Change From Baseline in Clinical Laboratory Hematology Parameter (Hematocrit) at Week 158 [Baseline, Week 158]

   Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Hematocrit levels were calculated as the ratio of the volume of red cells to the volume of whole blood. Change from baseline in hematocrit at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

5. Change From Baseline in Clinical Laboratory Hematology Parameter (Hemoglobin) at Week 158 [Baseline, Week 158]

   Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Change from baseline in hemoglobin at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

6. Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Alanine Aminotransferase and Alkaline Phosphatase) at Week 158 [Baseline, Week 158]

   Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in alanine aminotransferase and alkaline phosphatase at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

7. Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Aspartate Aminotransferase and Lactate Dehydrogenase) at Week 158 [Baseline, Week 158]

   Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in aspartate aminotransferase and lactate dehydrogenase at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

8. Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides) at Week 158 [Baseline, Week 158]

   Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium and triglycerides at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

9. Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Protein and Albumin) at Week 158 [Baseline, Week 158]

   Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in protein and albumin at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

10. Change From Baseline in Clinical Laboratory Serum Chemistry Parameter (Creatinine Clearance) at Week 106 [Baseline, Week 106]

    Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in creatinine clearance at baseline and Week 106 is reported in this outcome measure. Observed value at baseline and observed value at Week 106 were used to calculate the change from baseline value at Week 106.

11. Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bilirubin, Creatinine, Direct Bilirubin, and Urate) at Week 158 [Baseline, Week 158]

    Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in bilirubin, creatinine, direct bilirubin, and urate at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.

12. Change From Baseline in Blood Pressure at Week 171 [Baseline, Week 171]

    Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were assessed in seated/supine position. Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.

13. Change From Baseline in Heart Rate at Week 171 [Baseline, Week 171]

    Heart rate was assessed in seated/supine position. Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.

14. Change From Baseline in Respiration Rate at Week 171 [Baseline, Week 171]

    Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.

15. Change From Baseline in Body Temperature at Week 171 [Baseline, Week 171]

    Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.

16. Electrocardiogram (ECG) Parameter Value (Heart Rate) at Baseline and Week 8 [Baseline, Week 8]

    ECG parameters included heart rate, PR interval, QRS duration, QT interval and Fridericia's corrected QT interval (QTcF). Heart rate measured by ECG at Baseline and Week 8 is reported in this outcome measure.

17. ECG Parameter Value (PR Interval, QRS Duration, QT Interval, QTcF) at Baseline and Week 8 [Baseline, Week 8]

    ECG parameters included heart rate, PR interval, QRS duration, QT interval and QTcF. PR interval, QRS duration, QT interval and QTcF at Baseline and Week 8 is reported in this outcome measure.

18. Number of Participants With Clinically Significant Abnormalities in ECG Parameters [Baseline, Week 8]

    ECG parameters included heart rate, PR interval, QRS duration, QT interval and QTcF. Clinical significance was as as per Investigator's discretion.

19. Duration of Time to Achieve a Stable Dose of SD-809 ER [From Day 1 until the first day at which the participant was taking the dose level they were receiving at Week 8 (up to maximum 1284 days)]

    Duration of time to achieve stable dose of SD-809, defined as the number of days from Day 1 until the first day at which the participant was taking the dose level they were receiving at Week 8.

20. Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) -Dysarthria Score at Week 171 [Baseline, Week 171]

    The UPDRS is a comprehensive instrument used to assess the signs and symptoms of Parkinson's disease and includes patient and clinician-based assessments of motor, cognitive, and behavioral symptoms. The UPDRS-Dysarthria question pertaining to speech/dysarthria was used to monitor study participants for parkinsonism. Participants rated their responses on a scale ranging from 0 to 4, where 0 = normal; 1 = mildly affected, no difficulty being understood; 2 = moderately affected, sometimes asked to repeat statements; 3 = severely affected, frequently asked to repeat statements; 4 = unintelligible most of the time. Higher scores indicated greater impairment.

21. Change From Baseline in Barnes Akathisia Rating Scale (BARS) Summary Score at Week 171 [Baseline, Week 171]

    BARS is a rating scale for evaluation of drug-induced akathisia. It includes a summary score (objective assessment of akathisia and subjective measures [self-awareness and distress]) and a global clinical assessment. Objective akathisia rated on a scale of 0-3 (0=normal, occasional fidgety movements of limbs; 1=characteristic restless movements for less than half the time observed; 2= characteristic restless movements for at least half the time observed; 3=constant characteristic restless movements). Subjective measures included awareness of restlessness (rated on a scale of 0 [absence of inner restlessness] to 3 [awareness of intense compulsion to move]) and distress related to restlessness (rated on a scale of 0 [no distress] to 3 [severe distress]). Objective akathisia and subjective measures summed to yield summary score ranging from 0 (no akathisia and restlessness) to 9 (severe akathisia and restlessness), where higher scores indicated more akathisia and restlessness.

22. Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Assessment Score at Week 171 [Baseline, Week 171]

    BARS is a rating scale for evaluation of drug-induced akathisia. It includes a summary score (objective assessment of akathisia and subjective measures [self-awareness and distress]) and a global clinical assessment. Global clinical assessment rated on a scale ranging from 0 to 5, where 0=Absent. No evidence of awareness of restlessness; 1=Questionable. Non-specific inner tension and fidgety movements; 2=Mild akathisia. Awareness of restlessness in legs and/or inner restlessness worse when required to stand still. Fidgety movements present, but characteristic restless movements not necessarily observed; 3=Moderate akathisia. Awareness of restlessness combined with characteristic restless movements; 4=Marked akathisia. Subjective experience of restlessness includes a compulsive desire to walk or pace; 5=Severe akathisia. Strong compulsion to pace up and down most of the time. Constant restlessness associated with intense distress and insomnia. Higher scores indicated more akathisia.

23. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score at Week 171 [Baseline, Week 171]

    HADS is a self-administered instrument reliable for detecting states of depression and anxiety It includes 2 subscales: Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (HADS-D) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score ranged from 0 to 21 for each subscale; where higher score indicated greater severity of anxiety and depression symptoms.

24. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score at Week 171 [Baseline, Week 171]

    HADS is a self-administered instrument reliable for detecting states of depression and anxiety It includes 2 subscales: Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (HADS-D) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score ranged from 0 to 21 for each subscale; where higher score indicated greater severity of anxiety and depression symptoms.

25. Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 171 [Baseline, Week 171]

    ESS is a self-administered questionnaire comprised of 8 questions that provides a measure of a participant's general level of daytime sleepiness. Participants were asked to rate their usual chances of dozing off or falling asleep in different situations or activities that most people engage in as part of their daily lives (sitting and reading; watching TV; sitting inactive in a public place; as a passenger in a car for an hour without a break; lying down to rest in the afternoon when circumstances permit; sitting and talking to someone; sitting quietly after a lunch without alcohol; in a car, while stopped for a few minutes in traffic), on a 4-point Likert scale ranging from 0 to 3, where 0=no chance; 1=slight chance; 2=moderate chance; 3=high chance. Total ESS score is the sum of 8 item-scores and can range between 0 and 24 with a higher the score indicating a higher level of daytime sleepiness.

26. Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) [Baseline up to 1-week follow-up visit (up to approximately 3 years 9 months)]

    C-SSRS is a clinician rated assessment of suicidal behavior and ideation categorized as: Suicidal behavior=a "yes" response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, non-fatal suicide attempt, and completed suicide); Suicidal ideation=a "yes" response to any one of 5 suicidal ideation questions which includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior was reported.

27. Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 171 [Baseline, Week 171]

    MoCA is a validated rapid screening instrument for assessing mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation by using 30 questions test. Time to administer the MoCA© is approximately 10 minutes. The total possible score ranges from 0 (worst) to 30 (best) points; where higher scores indicate better cognitive function. A score of 26 or above is considered normal and a score below 26 is considered as recognitive dysfunction.

28. Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Behavior Score at Week 171 [Baseline, Week 171]

    The UHDRS is a research tool developed by the Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. The components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. The total behavior score is made up of subscores evaluating depressed mood, apathy, low self-esteem/guilt, compulsive behavior, anxiety, irritable behavior, perseverative/obsessive thinking, disruptive/aggressive behavior, suicidal thoughts, delusions, and hallucinations. For each subscore the frequency and severity was assessed separately. Frequency was rated on a scale of 0 (never or almost never) to 4 (very frequently, most of the time). Severity was rated on a scale of 0 (no evidence) to 4 (severe). Total behavior score ranges from 0 (no impairment) to 88 (severe impairment). Higher scores indicated greater behavioral impairments.

29. Change From Baseline in UHDRS Functional Assessment Score at Week 28 [Baseline, Week 28]

    The UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of the clinical features and course of HD. The components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Functional assessment included 25 questions with possible answers 'yes' or 'no'. Total score ranges from 0 (worst) to 25 (best). Higher scores indicate better functional ability.

30. Change From Baseline in UHDRS Independence Scale Score at Week 28 [Baseline, Week 28]

    UHDRS: research tool to provide a uniform assessment of clinical features and course of HD. Components of UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Independence scale ranges from 10-100, indicating most accurate current level of participant's independence. 10=Tube fed, total bed care; 20=No speech, must be fed; 30=Participant provides minimal assistance in own feeding,bathing,toileting; 40=Chronic care facility needed; limited self-feeding; 50=24-hour supervision appropriate; assistance required for bathing,eating,toileting; 60=Needs minor assistance in dressing,toileting,bathing; 70=Self-care maintained for bathing,limited household duties; unable to manage finances; 80=Pre-disease level of employment changes or ends; cannot perform household chores, may need help with finances; 90=No physical care needed(difficult tasks avoided); 100=No special care needed. Higher scores indicate better independence.

31. Change From Baseline in UHDRS Total Functional Capacity (TFC) Score at Week 132 [Baseline, Week 132]

    UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities (TFC). TFC is a 5-item clinician rating scale typically completed after a brief interview with a participant and/or collateral source. TFC globally assesses occupation, finances, domestic chores, activities of daily living, and level of care, with scores on each item ranging from 0 to either 2 or 3 (e.g., Occupation: 0 = unable, 1 = marginal work only, 2 = reduced capacity for usual job, 3 = normal). The five items are summed to yield a TFC total score, which ranges from 0 (normal function) to 13 (severe dysfunction). Higher scores indicated better functioning.

32. Change From Baseline in UHDRS Cognitive Assessment Score at Week 171 [Baseline, Week 171]

    Components of UHDRS assess motor function,cognition,behaviour,functional abilities,independence scale, total functional capacities. Cognitive assessment component:verbal fluency(VF) score (memory,attention)(requiring participant to generate as many words as possible beginning with a specific letter[F,A,S]in 60 seconds [sec]. Score[no range]:total number of correct words for 3 letters), symbol digit modalities test(SDMT) score(psychomotor speed,attention)(participant is required to pair digits to assigned symbols using a reference key. Score[0 {worst}-120 {best}]:total number of correct written responses in 90 sec), & Stroop interference(SI) score (selective attention,executive function)(includes 3 conditions:naming colour blocks[blue, red or green]; reading colour words printed in black ink; naming ink colour of incongruous colour words. For each condition score(no range)is number of correct responses produced in 45 sec). In these tests, higher scores reflect better cognitive ability.

33. Change From Baseline in UHDRS Motor Assessment: Total Maximal Chorea (TMC) Score at Week 171 [Baseline, Week 171]

    UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes total motor score (TMS) and TMC score. TMC score is determined from Item 12 (maximal chorea) of UHDRS TMS and quantifies chorea based on assessments of the face, bucco-oral-lingual area, trunk, and the 4 extremities. TMC score is a sum of chorea scores in the 7 body regions, ranging from 0 (absent chorea) to 28 (marked/prolonged chorea). Lower TMC scores indicated less chorea.

34. Change From Week 8 in UHDRS Motor Assessment: TMC Score at Week 171 [Week 8, Week 171]

    UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of clinical features and course of HD. Components of full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and TMC score. TMC score is determined from Item 12 (maximal chorea) of UHDRS TMS and quantifies chorea based on assessments of the face, bucco-oral-lingual area, trunk, and the 4 extremities. TMC score is a sum of chorea scores in the 7 body regions, ranging from 0(absent chorea) to 28 (marked/prolonged chorea). Lower TMC scores indicated less chorea. Data was measured and available for total safety population. Data was not available by individual cohorts (rollover cohort and switch cohort) from Week 8 to Week 171, as was done for change from baseline. Therefore, in order to present results data for this outcome measure, the total, combined safety population treatment arm was used.

35. Change From Baseline in UHDRS Motor Assessment: Total Motor Score (TMS) at Week 171 [Baseline, Week 171]

    UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and TMC score. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.

36. Change From Week 8 in UHDRS Motor Assessment: TMS at Week 171 [Week 8, Week 171]

    Components of full UHDRS assess motor function,cognition,behaviour,functional abilities,independence scale,total functional capacities. Motor function assessment includes TMS and TMC score. TMS assesses all motor features of HD and includes maximal chorea, maximal dystonia,ocular pursuit,saccade initiation and velocity,dysarthria,tongue protrusion,finger tapping,hand pronation and supination,luria rigidity,bradykinesia,gait,tandem walking,retropulsion pull test. Each of these was rated on a scale of 0(normal motor function) to 4(severely impaired motor function). TMS score is a sum of individual scores ranging from 0(normal motor function) to 124(severely impaired motor function). Lower TMS scores= better motor function. Data was available for total safety population, not by individual cohorts(rollover and switch cohort) from Week 8 to Week 171,as was done for change from baseline. Therefore, in order to present results data,the total,combined safety population treatment arm was used.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant is at least 18 years of age or the age of majority (whichever is older) at Screening.

• Participant has been diagnosed with manifest HD, as indicated by characteristic motor exam features, and has a documented expanded cytosine adenine guanine (CAG) repeat (greater than or equal to >= [37]) at or before Screening.

• Participant meets either of the following:

1. Has successfully completed participation in the First-HD Study (SD-809-C-15) or

2. Has been receiving an Food and Drug Administration (FDA)-approved dose of tetrabenazine that has been stable for >=8 weeks before Screening and is providing a therapeutic benefit for control of chorea.

• Participant has a Total Functional Capacity (TFC) score >=5 at Screening.

• Participant is able to swallow study medication whole.

• Participant has provided written, informed consent or, a legally authorized representative (LAR) has provided written informed consent and the subject has provided assent.

• Participant has provided a Research Advance Directive.

• Female participants of childbearing potential agree to use an acceptable method of contraception from screening through study completion.

• The participant has a reliable caregiver who interacts with the participant on a daily basis, oversees study drug administration, assures attendance at study visits and participates in evaluations, as required.

• Participant is able to ambulate without assistance for at least 20 yards (Note: The use of assistive devices (such as; walker, cane) are permitted during ambulation).

• Has sufficient reading skills to comprehend the participant completed rating scales.

Exclusion Criteria:

• Participant has a serious untreated or under-treated psychiatric illness, such as depression, at Screening or Baseline.

• Participant has active suicidal ideation at Screening or Baseline.

• Participant has history of suicidal behavior at Screening or Baseline.

• Participant has evidence for depression at Baseline.

• Participant has an unstable or serious medical illness at Screening or Baseline.

• Participant has received tetrabenazine within 7 days of Baseline (Rollover participants only).

• Participant has received any of the following concomitant medications within 30 days of Screening or Baseline: Antipsychotics, Metoclopramide, Monoamine oxidase inhibitors (MAOI), Levodopa or dopamine agonists, Reserpine, Amantadine, Memantine (Rollover participants only)

• Switch participants may receive Memantine if on a stable, approved dose for at least 30 days

• Participant has significantly impaired swallowing function at Screening or Baseline.

• Participant has significantly impaired speaking at Screening or Baseline.

• Participant requires treatment with drugs known to prolong the QT interval.

• Participant has prolonged QT interval on 12-lead electrocardiogram (ECG) at Screening.

• Participant has evidence of hepatic impairment at Screening.

• Participant has evidence of significant renal impairment at Screening.

• Participant has known allergy to any of the components of study medication.

• Participant has participated in an investigational drug or device trial other than SD-809-C-15 within 30 days (or 5 drug half-lives) of Screening, whichever is longer.

• Participant is pregnant or breast-feeding at Screening or Baseline.

• Participant acknowledges present use of illicit drugs at Screening or Baseline.

• Participant has a history of alcohol or substance abuse in the previous 12 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 057	Birmingham	Alabama	United States	35233
2	Teva Investigational Site 038	Phoenix	Arizona	United States	85013
3	Teva Investigational Site 298	Fayetteville	Arkansas	United States	72703
4	Teva Investigational Site 052	Englewood	Colorado	United States	80113
5	Teva Investigational Site 333	Washington	District of Columbia	United States	20007
6	Teva Investigational Site 160	Gainesville	Florida	United States	32607
7	Teva Investigational Site 014	Miami	Florida	United States	33136
8	Teva Investigational Site 032	Atlanta	Georgia	United States	30329
9	Teva Investigational Site 045	Indianapolis	Indiana	United States	46202
10	Teva Investigational Site 024	Iowa City	Iowa	United States	52242
11	Teva Investigational Site 029	Kansas City	Kansas	United States	66160
12	Teva Investigational Site 083	Wichita	Kansas	United States	67226
13	Teva Investigational Site 087	Louisville	Kentucky	United States	40202
14	Teva Investigational Site 028	Baltimore	Maryland	United States	21287
15	Teva Investigational Site 040	Boston	Massachusetts	United States	02118
16	Teva Investigational Site 027	Saint Louis	Missouri	United States	63110
17	Teva Investigational Site 194	Las Vegas	Nevada	United States	89102
18	Teva Investigational Site 328	Camden	New Jersey	United States	08103
19	Teva Investigational Site 026	New Brunswick	New Jersey	United States	08901
20	Teva Investigational Site 037	Albany	New York	United States	12208
21	Teva Investigational Site 002	New York	New York	United States	10032
22	Teva Investigational Site 342	Patchogue	New York	United States	11772
23	Teva Investigational Site 119	Durham	North Carolina	United States	27705
24	Teva Investigational Site 089	Cincinnati	Ohio	United States	45267
25	Teva Investigational Site 020	Columbus	Ohio	United States	43210
26	Teva Investigational Site 093	Toledo	Ohio	United States	43614-2598
27	Teva Investigational Site 341	Tulsa	Oklahoma	United States	74136
28	Teva Investigational Site 031	Nashville	Tennessee	United States	37232-2551
29	Teva Investigational Site 007	Houston	Texas	United States	77030
30	Teva Investigational Site 199	Houston	Texas	United States	77030
31	Teva Investigational Site 100	Salt Lake City	Utah	United States	84108
32	Teva Investigational Site 137	Burlington	Vermont	United States	05401
33	Teva Investigational Site 220	Kirkland	Washington	United States	98034
34	Teva Investigational Site 096	Seattle	Washington	United States	98108
35	Teva Investigational Site 054	Sydney		Australia	2145
36	Teva Investigational Site 098	Montreal		Canada	H2L4M1
37	Teva Investigational Site 231	Ottawa		Canada	K1G 3G4
38	Teva Investigational Site 300	Toronto		Canada	M2K 1E1

Sponsors and Collaborators

• Auspex Pharmaceuticals, Inc.

Investigators

• Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

• Study Protocol - Mar 2, 2015
• Statistical Analysis Plan - Sep 15, 2017

More Information

Publications

None provided.

• Responsible Party: Auspex Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01897896
• Other Study ID Numbers: SD-809-C-16
• First Posted: Jul 12, 2013
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Auspex Pharmaceuticals, Inc.: Chorea; Huntington Disease
• Additional relevant MeSH terms: Huntington Disease; Chorea

Study Results

Participant Flow

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo or SD-809 group [NCT01795859], including 1-week washout period and Week 13 evaluation), received 6 milligrams(mg) SD-809 ER tablet once daily as starting dose in this study. Dose titration was continued through Week 8 to optimize dose. SD-809 ER dose could be adjusted weekly in increments of 6 milligrams per day(mg/day) (6 or 12 mg/day after total daily dose of 48 mg reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day(36 mg twice daily), unless participant was receiving a strong CYP2D6 inhibitor(e.g., paroxetine,buproprion, fluoxetine), in which case maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving Food and Drug Administration (FDA) - approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state area under the curve(AUC) of total (alpha+beta)-Dihydrotetrabenazine(HTBZ) metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. SD-809 ER dose could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after total daily dose of 48 mg reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Period Title: Overall Study
STARTED	82	37
COMPLETED	56	25
NOT COMPLETED	26	12

Baseline Characteristics

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER	Total
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Total of all reporting groups
Overall Participants	82	37	119
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.7 (12.27)	52.4 (11.48)	53.3 (12.00)
Sex: Female, Male (Count of Participants)
Female	37 45.1%	15 40.5%	52 43.7%
Male	45 54.9%	22 59.5%	67 56.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 5.4%	2 1.7%
Not Hispanic or Latino	82 100%	35 94.6%	117 98.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	4 4.9%	0 0%	4 3.4%
White	76 92.7%	36 97.3%	112 94.1%
Other	0 0%	1 2.7%	1 0.8%
Multiple	2 2.4%	0 0%	2 1.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Entire Treatment Period
Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=inability to carry out usual activities. Drug-related TEAEs: TEAEs with possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline to follow-up visit (up to approximately 3 years 9 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Any TEAEs	77 93.9%	35 94.6%
Serious TEAEs	21 25.6%	11 29.7%
Severe TEAEs	17 20.7%	7 18.9%
Drug-Related TEAEs	56 68.3%	26 70.3%
TEAEs Leading to Withdrawal From Study	13 15.9%	3 8.1%

2. Primary Outcome

Title	Rollover Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Titration
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Day 1 to end of Week 8

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug.

Arm/Group Title	Rollover Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82
Any TEAEs	49 59.8%
Serious TEAEs	1 1.2%
Severe TEAEs	0 0%
Drug-Related TEAEs	23 28%
TEAEs Leading to Withdrawal From Study	0 0%

3. Primary Outcome

Title	Switch Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Dose Adjustment
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Day 1 to end of Week 4

Outcome Measure Data

Analysis Population Description

Safety population included all participants received at least 1 dose of study drug.

Arm/Group Title	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	37
Any TEAEs	17 20.7%
Serious TEAEs	1 1.2%
Severe TEAEs	1 1.2%
Drug-Related TEAEs	11 13.4%
TEAEs Leading to Withdrawal From Study	0 0%

4. Primary Outcome

Title	Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Long Term Stable Dose Treatment
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Week 8 to follow-up visit (up to approximately 3 years 9 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	81	35
Any TEAEs	74 90.2%	35 94.6%
Serious TEAEs	20 24.4%	10 27%
Severe TEAEs	17 20.7%	7 18.9%
Drug-Related TEAEs	49 59.8%	22 59.5%
TEAEs Leading to Withdrawal From Study	13 15.9%	3 8.1%

5. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets) at Week 158
Description	Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Change from baseline in basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets cells at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed values at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Basophils: Baseline	0.029 (0.0231)	0.035 (0.0283)
Basophils: Change at Week 158	-0.014 (0.0287)	-0.004 (0.0385)
Eosinophils: Baseline	0.151 (0.1274)	0.195 (0.1366)
Eosinophils: Change at Week 158	-0.054 (0.0784)	0.009 (0.0911)
Leukocytes: Baseline	6.98 (2.083)	6.97 (1.828)
Leukocytes: Change at Week 158	-0.04 (0.927)	-0.04 (1.098)
Lymphocytes: Baseline	1.922 (0.7674)	1.789 (0.7088)
Lymphocytes: Change at Week 158	-0.088 (0.4261)	0.075 (0.5409)
Monocytes: Baseline	0.445 (0.1805)	0.416 (0.1416)
Monocytes: Change at Week 158	-0.129 (0.1722)	-0.068 (0.1335)
Neutrophils: Baseline	4.437 (1.6324)	4.538 (1.4741)
Neutrophils: Change at Week 158	0.243 (0.6359)	-0.050 (0.8166)
Platelets: Baseline	235.6 (62.81)	247.2 (77.63)
Platelets: Change at Week 158	1.2 (56.09)	-12.0 (26.59)

6. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes Mean Corpuscular Volume) at Week 158
Description	Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Change from baseline in erythrocytes mean corpuscular volume at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	91.1 (3.95)	92.1 (5.39)
Change at Week 158	2.2 (3.23)	1.6 (4.14)

7. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes) at Week 158
Description	Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Change from baseline in erythrocytes at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	4.60 (0.397)	4.54 (0.377)
Change at Week 158	0.18 (0.262)	0.19 (0.247)

8. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Hematology Parameter (Hematocrit) at Week 158
Description	Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Hematocrit levels were calculated as the ratio of the volume of red cells to the volume of whole blood. Change from baseline in hematocrit at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	0.419 (0.0363)	0.417 (0.0397)
Change at Week 158	0.025 (0.0255)	0.025 (0.0334)

9. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Hematology Parameter (Hemoglobin) at Week 158
Description	Clinical laboratory hematology parameters included basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils, platelets, erythrocytes mean corpuscular volume, erythrocytes, hematocrit, and hemoglobin. Change from baseline in hemoglobin at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	139.7 (12.26)	138.4 (13.19)
Change at Week 158	4.6 (7.99)	4.5 (11.99)

10. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Alanine Aminotransferase and Alkaline Phosphatase) at Week 158
Description	Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in alanine aminotransferase and alkaline phosphatase at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Alanine Aminotransferase: Baseline	20.7 (9.74)	18.9 (12.20)
Alanine Aminotransferase: Change at Week 158	-5.3 (7.51)	-2.1 (9.74)
Alkaline Phosphatase: Baseline	72.6 (20.24)	73.1 (20.61)
Alkaline Phosphatase: Change at Week 158	-1.0 (8.21)	1.0 (9.62)

11. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Aspartate Aminotransferase and Lactate Dehydrogenase) at Week 158
Description	Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in aspartate aminotransferase and lactate dehydrogenase at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Aspartate Aminotransferase: Baseline	20.5 (5.84)	18.4 (6.88)
Aspartate Aminotransferase: Change at Week 158	-2.7 (5.43)	-1.1 (5.40)
Lactate Dehydrogenase: Baseline	163.9 (28.05)	161.1 (42.32)
Lactate Dehydrogenase: Change at Week 158	-5.5 (27.83)	-4.9 (18.45)

12. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides) at Week 158
Description	Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium and triglycerides at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Bicarbonate: Baseline	24.7 (2.55)	24.7 (2.06)
Bicarbonate: Change at Week 158	-0.2 (2.87)	0.7 (3.16)
Blood Urea Nitrogen: Baseline	5.979 (1.8432)	6.282 (1.8177)
Blood Urea Nitrogen: Change at Week 158	-0.531 (1.4864)	-0.323 (0.9797)
Calcium: Baseline	2.417 (0.1067)	2.393 (0.1523)
Calcium: Change at Week 158	-0.034 (0.1282)	-0.067 (0.0869)
Chloride: Baseline	102.5 (2.28)	103.8 (2.24)
Chloride: Change at Week 158	-2.7 (2.62)	-2.0 (1.50)
Cholesterol: Baseline	5.118 (0.9505)	4.863 (1.1686)
Cholesterol: Change at Week 158	-0.131 (0.8790)	-0.173 (0.7715)
Glucose: Baseline	5.28 (1.571)	5.31 (1.029)
Glucose: Change at Week 158	-0.54 (1.018)	-0.64 (1.033)
Magnesium: Baseline	0.871 (0.0566)	0.843 (0.0567)
Magnesium: Change at Week 158	-0.027 (0.0701)	0.016 (0.0639)
Phosphate: Baseline	1.194 (0.1769)	1.191 (0.1661)
Phosphate: Change at Week 158	-0.029 (0.2298)	0.061 (0.1330)
Potassium: Baseline	4.39 (0.419)	4.46 (0.332)
Potassium: Change at Week 158	-0.14 (0.414)	0.19 (0.501)
Sodium: Baseline	142.4 (2.14)	142.9 (2.31)
Sodium: Change at Week 158	-2.0 (3.56)	-1.7 (2.06)
Triglycerides: Baseline	1.606 (1.0001)	1.733 (1.2887)
Triglycerides: Change at Week 158	-0.147 (0.8692)	-0.420 (1.0005)

13. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Protein and Albumin) at Week 158
Description	Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in protein and albumin at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Protein: Baseline	69.5 (3.88)	67.3 (4.54)
Protein: Change at Week 158	-0.9 (3.54)	-2.9 (4.43)
Albumin: Baseline	43.9 (2.55)	43.1 (2.65)
Albumin: Change at Week 158	0.2 (3.61)	-0.9 (2.57)

14. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Serum Chemistry Parameter (Creatinine Clearance) at Week 106
Description	Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in creatinine clearance at baseline and Week 106 is reported in this outcome measure. Observed value at baseline and observed value at Week 106 were used to calculate the change from baseline value at Week 106.
Time Frame	Baseline, Week 106

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	94.1 (26.67)	89.9 (27.55)
Change at Week 106	-4.5 (6.36)	-34.0

15. Secondary Outcome

Title	Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bilirubin, Creatinine, Direct Bilirubin, and Urate) at Week 158
Description	Clinical laboratory serum chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, glucose, magnesium, phosphate, potassium, sodium, triglycerides, protein, albumin, creatinine clearance, bilirubin, creatinine, direct bilirubin, and urate. Change from baseline in bilirubin, creatinine, direct bilirubin, and urate at baseline and Week 158 is reported in this outcome measure. Observed value at baseline and observed value at Week 158 were used to calculate the change from baseline value at Week 158.
Time Frame	Baseline, Week 158

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Bilirubin: Baseline	7.8 (4.82)	6.0 (2.43)
Bilirubin: Change at Week 158	-0.7 (2.51)	-1.4 (2.07)
Creatinine: Baseline	82.8 (16.81)	84.2 (19.02)
Creatinine: Change at Week 158	-2.4 (10.13)	-2.4 (6.46)
Direct Bilirubin: Baseline	2.4 (0.94)	2.1 (0.35)
Direct Bilirubin: Change at Week 158	0.1 (0.23)	-0.2 (0.44)
Urate: Baseline	305.2 (83.70)	269.5 (75.06)
Urate: Change at Week 158	-21.8 (55.50)	-3.4 (39.37)

16. Secondary Outcome

Title	Change From Baseline in Blood Pressure at Week 171
Description	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were assessed in seated/supine position. Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
SBP: Baseline	120.5 (12.70)	118.9 (17.80)
SBP: Change at Week 171	-4.0
DBP: Baseline	73.3 (10.21)	73.8 (11.85)
DBP: Change at Week 171	-6.0

17. Secondary Outcome

Title	Change From Baseline in Heart Rate at Week 171
Description	Heart rate was assessed in seated/supine position. Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	70.7 (8.68)	68.1 (12.56)
Change at Week 171	25.0

18. Secondary Outcome

Title	Change From Baseline in Respiration Rate at Week 171
Description	Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	16.4 (2.57)	17.5 (2.58)
Change at Week 171	-1.3 (2.06)	-3.5 (3.54)

19. Secondary Outcome

Title	Change From Baseline in Body Temperature at Week 171
Description	Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	36.56 (0.427)	36.67 (0.309)
Change at Week 171	-0.13 (0.468)	-0.10 (0.283)

20. Secondary Outcome

Title	Electrocardiogram (ECG) Parameter Value (Heart Rate) at Baseline and Week 8
Description	ECG parameters included heart rate, PR interval, QRS duration, QT interval and Fridericia's corrected QT interval (QTcF). Heart rate measured by ECG at Baseline and Week 8 is reported in this outcome measure.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	67.4 (9.87)	63.8 (13.96)
Week 8	64.6 (9.22)	65.8 (13.50)

21. Secondary Outcome

Title	ECG Parameter Value (PR Interval, QRS Duration, QT Interval, QTcF) at Baseline and Week 8
Description	ECG parameters included heart rate, PR interval, QRS duration, QT interval and QTcF. PR interval, QRS duration, QT interval and QTcF at Baseline and Week 8 is reported in this outcome measure.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
PR Interval: Baseline	164.1 (25.03)	159.5 (22.65)
PR Interval: Week 8	165.2 (23.87)	155.7 (18.08)
QRS Duration: Baseline	92.8 (14.37)	88.8 (10.16)
QRS Duration: Week 8	91.0 (12.09)	88.0 (10.97)
QT Interval: Baseline	399.8 (27.44)	415.6 (37.44)
QT Interval: Week 8	405.1 (29.10)	404.5 (35.43)
QTcF: Baseline	413.3 (18.67)	419.3 (17.89)
QTcF: Week 8	412.7 (20.10)	412.8 (18.05)

22. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in ECG Parameters
Description	ECG parameters included heart rate, PR interval, QRS duration, QT interval and QTcF. Clinical significance was as as per Investigator's discretion.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	5 6.1%	0 0%
Week 8	2 2.4%	0 0%

23. Secondary Outcome

Title	Duration of Time to Achieve a Stable Dose of SD-809 ER
Description	Duration of time to achieve stable dose of SD-809, defined as the number of days from Day 1 until the first day at which the participant was taking the dose level they were receiving at Week 8.
Time Frame	From Day 1 until the first day at which the participant was taking the dose level they were receiving at Week 8 (up to maximum 1284 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	81	35
Median (Full Range) [days]	47.0	28.0

24. Secondary Outcome

Title	Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) -Dysarthria Score at Week 171
Description	The UPDRS is a comprehensive instrument used to assess the signs and symptoms of Parkinson's disease and includes patient and clinician-based assessments of motor, cognitive, and behavioral symptoms. The UPDRS-Dysarthria question pertaining to speech/dysarthria was used to monitor study participants for parkinsonism. Participants rated their responses on a scale ranging from 0 to 4, where 0 = normal; 1 = mildly affected, no difficulty being understood; 2 = moderately affected, sometimes asked to repeat statements; 3 = severely affected, frequently asked to repeat statements; 4 = unintelligible most of the time. Higher scores indicated greater impairment.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	0.9 (0.79)	1.1 (0.74)
Change at Week 171	0.4 (0.79)	1.5 (0.71)

25. Secondary Outcome

Title	Change From Baseline in Barnes Akathisia Rating Scale (BARS) Summary Score at Week 171
Description	BARS is a rating scale for evaluation of drug-induced akathisia. It includes a summary score (objective assessment of akathisia and subjective measures [self-awareness and distress]) and a global clinical assessment. Objective akathisia rated on a scale of 0-3 (0=normal, occasional fidgety movements of limbs; 1=characteristic restless movements for less than half the time observed; 2= characteristic restless movements for at least half the time observed; 3=constant characteristic restless movements). Subjective measures included awareness of restlessness (rated on a scale of 0 [absence of inner restlessness] to 3 [awareness of intense compulsion to move]) and distress related to restlessness (rated on a scale of 0 [no distress] to 3 [severe distress]). Objective akathisia and subjective measures summed to yield summary score ranging from 0 (no akathisia and restlessness) to 9 (severe akathisia and restlessness), where higher scores indicated more akathisia and restlessness.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	1.1 (1.67)	0.8 (1.25)
Change at Week 171	0.7 (1.50)	0.5 (3.54)

26. Secondary Outcome

Title	Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Assessment Score at Week 171
Description	BARS is a rating scale for evaluation of drug-induced akathisia. It includes a summary score (objective assessment of akathisia and subjective measures [self-awareness and distress]) and a global clinical assessment. Global clinical assessment rated on a scale ranging from 0 to 5, where 0=Absent. No evidence of awareness of restlessness; 1=Questionable. Non-specific inner tension and fidgety movements; 2=Mild akathisia. Awareness of restlessness in legs and/or inner restlessness worse when required to stand still. Fidgety movements present, but characteristic restless movements not necessarily observed; 3=Moderate akathisia. Awareness of restlessness combined with characteristic restless movements; 4=Marked akathisia. Subjective experience of restlessness includes a compulsive desire to walk or pace; 5=Severe akathisia. Strong compulsion to pace up and down most of the time. Constant restlessness associated with intense distress and insomnia. Higher scores indicated more akathisia.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	0.5 (0.83)	0.4 (0.68)
Change at Week 171	0.4 (0.79)	1.0 (1.41)

27. Secondary Outcome

Title	Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score at Week 171
Description	HADS is a self-administered instrument reliable for detecting states of depression and anxiety It includes 2 subscales: Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (HADS-D) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score ranged from 0 to 21 for each subscale; where higher score indicated greater severity of anxiety and depression symptoms.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	2.7 (2.99)	4.3 (3.45)
Change at Week 171	1.3 (2.63)	-2.5 (2.12)

28. Secondary Outcome

Title	Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score at Week 171
Description	HADS is a self-administered instrument reliable for detecting states of depression and anxiety It includes 2 subscales: Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (HADS-D) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score ranged from 0 to 21 for each subscale; where higher score indicated greater severity of anxiety and depression symptoms.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	2.0 (2.47)	3.4 (2.54)
Change at Week 171	2.4 (5.26)	2.0 (4.24)

29. Secondary Outcome

Title	Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 171
Description	ESS is a self-administered questionnaire comprised of 8 questions that provides a measure of a participant's general level of daytime sleepiness. Participants were asked to rate their usual chances of dozing off or falling asleep in different situations or activities that most people engage in as part of their daily lives (sitting and reading; watching TV; sitting inactive in a public place; as a passenger in a car for an hour without a break; lying down to rest in the afternoon when circumstances permit; sitting and talking to someone; sitting quietly after a lunch without alcohol; in a car, while stopped for a few minutes in traffic), on a 4-point Likert scale ranging from 0 to 3, where 0=no chance; 1=slight chance; 2=moderate chance; 3=high chance. Total ESS score is the sum of 8 item-scores and can range between 0 and 24 with a higher the score indicating a higher level of daytime sleepiness.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	4.4 (3.72)	6.0 (4.15)
Change at Week 171	4.7 (7.45)	1.0 (1.41)

30. Secondary Outcome

Title	Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS)
Description	C-SSRS is a clinician rated assessment of suicidal behavior and ideation categorized as: Suicidal behavior=a "yes" response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, non-fatal suicide attempt, and completed suicide); Suicidal ideation=a "yes" response to any one of 5 suicidal ideation questions which includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior was reported.
Time Frame	Baseline up to 1-week follow-up visit (up to approximately 3 years 9 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	81	37
Suicidal Ideation	11 13.4%	4 10.8%
Suicidal Behavior	3 3.7%	1 2.7%
Self-injurious behavior without suicidal intent	1 1.2%	0 0%

31. Secondary Outcome

Title	Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 171
Description	MoCA is a validated rapid screening instrument for assessing mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation by using 30 questions test. Time to administer the MoCA© is approximately 10 minutes. The total possible score ranges from 0 (worst) to 30 (best) points; where higher scores indicate better cognitive function. A score of 26 or above is considered normal and a score below 26 is considered as recognitive dysfunction.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	23.9 (4.35)	21.9 (3.86)
Change at Week 171	-3.1 (4.81)	4.5 (3.54)

32. Secondary Outcome

Title	Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Behavior Score at Week 171
Description	The UHDRS is a research tool developed by the Huntington Disease (HD) Study Group to provide a uniform assessment of the clinical features and course of HD. The components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. The total behavior score is made up of subscores evaluating depressed mood, apathy, low self-esteem/guilt, compulsive behavior, anxiety, irritable behavior, perseverative/obsessive thinking, disruptive/aggressive behavior, suicidal thoughts, delusions, and hallucinations. For each subscore the frequency and severity was assessed separately. Frequency was rated on a scale of 0 (never or almost never) to 4 (very frequently, most of the time). Severity was rated on a scale of 0 (no evidence) to 4 (severe). Total behavior score ranges from 0 (no impairment) to 88 (severe impairment). Higher scores indicated greater behavioral impairments.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	7.1 (8.26)	10.9 (10.66)
Change at Week 171	8.6 (12.47)	4.5 (2.12)

33. Secondary Outcome

Title	Change From Baseline in UHDRS Functional Assessment Score at Week 28
Description	The UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of the clinical features and course of HD. The components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Functional assessment included 25 questions with possible answers 'yes' or 'no'. Total score ranges from 0 (worst) to 25 (best). Higher scores indicate better functional ability.
Time Frame	Baseline, Week 28

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	21.4 (3.00)	18.2 (4.94)
Change at Week 28	-1.6 (2.76)	-1.6 (3.62)

34. Secondary Outcome

Title	Change From Baseline in UHDRS Independence Scale Score at Week 28
Description	UHDRS: research tool to provide a uniform assessment of clinical features and course of HD. Components of UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Independence scale ranges from 10-100, indicating most accurate current level of participant's independence. 10=Tube fed, total bed care; 20=No speech, must be fed; 30=Participant provides minimal assistance in own feeding,bathing,toileting; 40=Chronic care facility needed; limited self-feeding; 50=24-hour supervision appropriate; assistance required for bathing,eating,toileting; 60=Needs minor assistance in dressing,toileting,bathing; 70=Self-care maintained for bathing,limited household duties; unable to manage finances; 80=Pre-disease level of employment changes or ends; cannot perform household chores, may need help with finances; 90=No physical care needed(difficult tasks avoided); 100=No special care needed. Higher scores indicate better independence.
Time Frame	Baseline, Week 28

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	84.0 (9.48)	75.5 (11.59)
Change at Week 28	-4.2 (9.60)	-1.2 (8.93)

35. Secondary Outcome

Title	Change From Baseline in UHDRS Total Functional Capacity (TFC) Score at Week 132
Description	UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities (TFC). TFC is a 5-item clinician rating scale typically completed after a brief interview with a participant and/or collateral source. TFC globally assesses occupation, finances, domestic chores, activities of daily living, and level of care, with scores on each item ranging from 0 to either 2 or 3 (e.g., Occupation: 0 = unable, 1 = marginal work only, 2 = reduced capacity for usual job, 3 = normal). The five items are summed to yield a TFC total score, which ranges from 0 (normal function) to 13 (severe dysfunction). Higher scores indicated better functioning.
Time Frame	Baseline, Week 132

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	9.6 (2.17)	8.3 (2.11)
Change at Week 132	-3.1 (2.86)	-3.1 (2.71)

36. Secondary Outcome

Title	Change From Baseline in UHDRS Cognitive Assessment Score at Week 171
Description	Components of UHDRS assess motor function,cognition,behaviour,functional abilities,independence scale, total functional capacities. Cognitive assessment component:verbal fluency(VF) score (memory,attention)(requiring participant to generate as many words as possible beginning with a specific letter[F,A,S]in 60 seconds [sec]. Score[no range]:total number of correct words for 3 letters), symbol digit modalities test(SDMT) score(psychomotor speed,attention)(participant is required to pair digits to assigned symbols using a reference key. Score[0 {worst}-120 {best}]:total number of correct written responses in 90 sec), & Stroop interference(SI) score (selective attention,executive function)(includes 3 conditions:naming colour blocks[blue, red or green]; reading colour words printed in black ink; naming ink colour of incongruous colour words. For each condition score(no range)is number of correct responses produced in 45 sec). In these tests, higher scores reflect better cognitive ability.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
VF Score: Baseline	25.1 (11.00)	21.5 (10.79)
VF Score: Change at Week 171	-10.9 (10.12)	4.0 (5.66)
SDMT: Baseline	24.4 (8.91)	22.7 (17.38)
SDMT: Change at Week 171	-9.6 (7.04)	0.0 (7.07)
SI Score: Baseline	3.2 (10.87)	-0.5 (6.38)
SI Score: Change at Week 171	-2.4 (7.42)	6.5 (4.27)

37. Secondary Outcome

Title	Change From Baseline in UHDRS Motor Assessment: Total Maximal Chorea (TMC) Score at Week 171
Description	UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes total motor score (TMS) and TMC score. TMC score is determined from Item 12 (maximal chorea) of UHDRS TMS and quantifies chorea based on assessments of the face, bucco-oral-lingual area, trunk, and the 4 extremities. TMC score is a sum of chorea scores in the 7 body regions, ranging from 0 (absent chorea) to 28 (marked/prolonged chorea). Lower TMC scores indicated less chorea.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	12.04 (4.113)	12.46 (5.221)
Change at Week 171	-3.71 (7.544)	4.75 (1.061)

38. Secondary Outcome

Title	Change From Week 8 in UHDRS Motor Assessment: TMC Score at Week 171
Description	UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of clinical features and course of HD. Components of full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and TMC score. TMC score is determined from Item 12 (maximal chorea) of UHDRS TMS and quantifies chorea based on assessments of the face, bucco-oral-lingual area, trunk, and the 4 extremities. TMC score is a sum of chorea scores in the 7 body regions, ranging from 0(absent chorea) to 28 (marked/prolonged chorea). Lower TMC scores indicated less chorea. Data was measured and available for total safety population. Data was not available by individual cohorts (rollover cohort and switch cohort) from Week 8 to Week 171, as was done for change from baseline. Therefore, in order to present results data for this outcome measure, the total, combined safety population treatment arm was used.
Time Frame	Week 8, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Combined Cohort (Rollover and Switch): SD-809 ER
Arm/Group Description	Participants of rollover cohort and switch cohort were included in this arm for the purpose of reporting data of this outcome measure.
Measure Participants	119
Week 8	8.5 (4.67)
Change at Week 171	2.4 (5.00)

39. Secondary Outcome

Title	Change From Baseline in UHDRS Motor Assessment: Total Motor Score (TMS) at Week 171
Description	UHDRS is a research tool developed by HD Study Group to provide a uniform assessment of the clinical features and course of HD. Components of the full UHDRS assess motor function, cognition, behaviour, functional abilities, independence scale and total functional capacities. Motor function assessment includes TMS and TMC score. The UHDRS TMS assesses all the motor features of HD and includes maximal chorea, maximal dystonia, ocular pursuit, saccade initiation and velocity, dysarthria, tongue protrusion, finger tapping, hand pronation and supination, luria, rigidity, bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these was rated on a scale of 0 (normal motor function) to 4 (severely impaired motor function). TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function). Lower TMS scores indicate better motor function.
Time Frame	Baseline, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Rollover Cohort: SD-809 ER	Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.	Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
Measure Participants	82	37
Baseline	34.67 (16.119)	37.76 (18.605)
Change at Week 171	11.29 (14.762)	18.50 (3.536)

40. Secondary Outcome

Title	Change From Week 8 in UHDRS Motor Assessment: TMS at Week 171
Description	Components of full UHDRS assess motor function,cognition,behaviour,functional abilities,independence scale,total functional capacities. Motor function assessment includes TMS and TMC score. TMS assesses all motor features of HD and includes maximal chorea, maximal dystonia,ocular pursuit,saccade initiation and velocity,dysarthria,tongue protrusion,finger tapping,hand pronation and supination,luria rigidity,bradykinesia,gait,tandem walking,retropulsion pull test. Each of these was rated on a scale of 0(normal motor function) to 4(severely impaired motor function). TMS score is a sum of individual scores ranging from 0(normal motor function) to 124(severely impaired motor function). Lower TMS scores= better motor function. Data was available for total safety population, not by individual cohorts(rollover and switch cohort) from Week 8 to Week 171,as was done for change from baseline. Therefore, in order to present results data,the total,combined safety population treatment arm was used.
Time Frame	Week 8, Week 171

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Combined Cohort (Rollover and Switch): SD-809 ER
Arm/Group Description	Participants of rollover cohort and switch cohort were included in this arm for the purpose of reporting data of this outcome measure.
Measure Participants	119
Week 8	30.7 (17.40)
Change at Week 171	22.2 (12.02)

Adverse Events

Time Frame	Baseline to follow-up visit (up to approximately 3 years 9 months)
Adverse Event Reporting Description	Safety population included all participants who received at least 1 dose of study drug.
Arm/Group Title	Rollover Cohort: SD-809 ER		Switch Cohort: SD-809 ER
Arm/Group Description	Participants who completed study SD-809-C-15 (either placebo group or SD-809 group, including 1-week washout period and Week 13 evaluation), received 6 mg SD-809 ER tablet once daily as a starting dose in this study. Dose titration was continued through Week 8 to optimize the dose. Dose of SD-809 ER could be adjusted weekly in increments of 6 mg/day (6 or 12 mg/day after a total daily dose of 48 mg was reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher were administered twice daily. Maximum total daily dose of SD-809 ER was 72 mg/day (36 mg twice daily), unless the participant was receiving a strong CYP2D6 inhibitor (e.g., paroxetine, buproprion, and fluoxetine), in which case the maximum total daily dose was 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.		Participants who were receiving FDA-approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, were converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state AUC of total (alpha+beta)-HTBZ metabolites that was predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants remained on initial dose of SD-809 ER through Week 1. Dose adjustment was continued through Week 4 to optimize the dose. Dose of SD-809 ER could be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg was reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments were permitted, if clinically indicated) continued until SD-809 ER became commercially available in United States.
All Cause Mortality
	Rollover Cohort: SD-809 ER		Switch Cohort: SD-809 ER
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/82 (1.2%)		0/37 (0%)
Serious Adverse Events
	Rollover Cohort: SD-809 ER		Switch Cohort: SD-809 ER
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/82 (25.6%)		11/37 (29.7%)
Gastrointestinal disorders
Intestinal obstruction	0/82 (0%)	0	1/37 (2.7%)	1
General disorders
Chest discomfort	1/82 (1.2%)	1	0/37 (0%)	0
Sudden cardiac death	1/82 (1.2%)	1	0/37 (0%)	0
Infections and infestations
Actinomycotic pulmonary infection	0/82 (0%)	0	1/37 (2.7%)	1
Appendicitis	1/82 (1.2%)	1	0/37 (0%)	0
Cellulitis staphylococcal	0/82 (0%)	0	1/37 (2.7%)	1
Gastroenteritis	0/82 (0%)	0	1/37 (2.7%)	1
Infection	1/82 (1.2%)	1	0/37 (0%)	0
Pneumonia	0/82 (0%)	0	2/37 (5.4%)	2
Pyelonephritis acute	0/82 (0%)	0	1/37 (2.7%)	1
Urinary tract infection bacterial	1/82 (1.2%)	1	0/37 (0%)	0
Injury, poisoning and procedural complications
Fall	1/82 (1.2%)	1	1/37 (2.7%)	1
Head injury	0/82 (0%)	0	1/37 (2.7%)	1
Hip fracture	1/82 (1.2%)	1	0/37 (0%)	0
Subdural haematoma	1/82 (1.2%)	1	0/37 (0%)	0
Upper limb fracture	1/82 (1.2%)	1	0/37 (0%)	0
Investigations
Weight decreased	0/82 (0%)	0	1/37 (2.7%)	1
Metabolism and nutrition disorders
Dehydration	2/82 (2.4%)	2	1/37 (2.7%)	1
Failure to thrive	0/82 (0%)	0	1/37 (2.7%)	1
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/82 (1.2%)	1	0/37 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Penile cancer	1/82 (1.2%)	1	0/37 (0%)	0
Renal oncocytoma	1/82 (1.2%)	1	0/37 (0%)	0
Nervous system disorders
Encephalopathy	1/82 (1.2%)	1	0/37 (0%)	0
Lethargy	1/82 (1.2%)	1	0/37 (0%)	0
Subarachnoid haemorrhage	1/82 (1.2%)	1	0/37 (0%)	0
Syncope	1/82 (1.2%)	1	1/37 (2.7%)	1
Psychiatric disorders
Aggression	1/82 (1.2%)	2	0/37 (0%)	0
Anxiety	1/82 (1.2%)	1	0/37 (0%)	0
Depression	0/82 (0%)	0	1/37 (2.7%)	1
Depression suicidal	1/82 (1.2%)	1	0/37 (0%)	0
Major depression	1/82 (1.2%)	1	0/37 (0%)	0
Mental status changes	1/82 (1.2%)	1	0/37 (0%)	0
Suicidal ideation	1/82 (1.2%)	1	0/37 (0%)	0
Suicide attempt	2/82 (2.4%)	2	0/37 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/82 (1.2%)	1	0/37 (0%)	0
Pulmonary embolism	1/82 (1.2%)	1	0/37 (0%)	0
Surgical and medical procedures
Spinal fusion surgery	1/82 (1.2%)	1	0/37 (0%)	0
Vascular disorders
Deep vein thrombosis	1/82 (1.2%)	1	0/37 (0%)	0
Other (Not Including Serious) Adverse Events
	Rollover Cohort: SD-809 ER		Switch Cohort: SD-809 ER
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/82 (90.2%)		32/37 (86.5%)
Cardiac disorders
Bradycardia	0/82 (0%)	0	2/37 (5.4%)	2
Ear and labyrinth disorders
Cerumen impaction	0/82 (0%)	0	2/37 (5.4%)	2
Eye disorders
Dry eye	0/82 (0%)	0	2/37 (5.4%)	2
Gastrointestinal disorders
Constipation	7/82 (8.5%)	7	5/37 (13.5%)	6
Diarrhoea	11/82 (13.4%)	13	7/37 (18.9%)	11
Dry mouth	4/82 (4.9%)	4	4/37 (10.8%)	4
Dysphagia	7/82 (8.5%)	12	6/37 (16.2%)	7
Gastrooesophageal reflux disease	1/82 (1.2%)	1	2/37 (5.4%)	2
Nausea	8/82 (9.8%)	8	3/37 (8.1%)	3
Vomiting	7/82 (8.5%)	10	2/37 (5.4%)	2
General disorders
Chest pain	2/82 (2.4%)	2	2/37 (5.4%)	2
Fatigue	7/82 (8.5%)	8	2/37 (5.4%)	2
Gait disturbance	4/82 (4.9%)	5	2/37 (5.4%)	3
Irritability	11/82 (13.4%)	13	4/37 (10.8%)	5
Oedema peripheral	0/82 (0%)	0	2/37 (5.4%)	2
Pyrexia	1/82 (1.2%)	1	2/37 (5.4%)	2
Infections and infestations
Bronchitis	5/82 (6.1%)	5	2/37 (5.4%)	2
Nasopharyngitis	8/82 (9.8%)	11	6/37 (16.2%)	8
Pneumonia	1/82 (1.2%)	1	5/37 (13.5%)	5
Sinusitis	3/82 (3.7%)	3	2/37 (5.4%)	3
Upper respiratory tract infection	2/82 (2.4%)	2	2/37 (5.4%)	3
Urinary tract infection	12/82 (14.6%)	18	4/37 (10.8%)	5
Injury, poisoning and procedural complications
Contusion	7/82 (8.5%)	11	1/37 (2.7%)	1
Fall	30/82 (36.6%)	78	15/37 (40.5%)	27
Laceration	7/82 (8.5%)	10	5/37 (13.5%)	9
Investigations
Weight decreased	11/82 (13.4%)	12	8/37 (21.6%)	8
Metabolism and nutrition disorders
Decreased appetite	1/82 (1.2%)	1	4/37 (10.8%)	5
Dehydration	3/82 (3.7%)	3	2/37 (5.4%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	4/82 (4.9%)	5	2/37 (5.4%)	3
Back pain	4/82 (4.9%)	4	2/37 (5.4%)	2
Nervous system disorders
Akathisia	5/82 (6.1%)	5	4/37 (10.8%)	5
Balance disorder	0/82 (0%)	0	2/37 (5.4%)	2
Chorea	7/82 (8.5%)	7	7/37 (18.9%)	10
Cognitive disorder	3/82 (3.7%)	4	2/37 (5.4%)	2
Headache	6/82 (7.3%)	7	1/37 (2.7%)	1
Memory impairment	3/82 (3.7%)	3	2/37 (5.4%)	2
Parkinsonism	3/82 (3.7%)	3	3/37 (8.1%)	4
Somnolence	16/82 (19.5%)	22	11/37 (29.7%)	16
Psychiatric disorders
Agitation	3/82 (3.7%)	3	3/37 (8.1%)	3
Anxiety	22/82 (26.8%)	32	13/37 (35.1%)	14
Apathy	5/82 (6.1%)	6	1/37 (2.7%)	1
Depressed mood	0/82 (0%)	0	2/37 (5.4%)	3
Depression	26/82 (31.7%)	35	7/37 (18.9%)	8
Insomnia	19/82 (23.2%)	23	6/37 (16.2%)	7
Sleep disorder	5/82 (6.1%)	6	1/37 (2.7%)	1
Suicidal ideation	4/82 (4.9%)	6	2/37 (5.4%)	2
Renal and urinary disorders
Micturition urgency	3/82 (3.7%)	3	2/37 (5.4%)	2
Pollakiuria	7/82 (8.5%)	7	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Choking	1/82 (1.2%)	1	3/37 (8.1%)	4
Skin and subcutaneous tissue disorders
Dermatitis contact	1/82 (1.2%)	1	2/37 (5.4%)	2
Hyperhidrosis	1/82 (1.2%)	1	2/37 (5.4%)	3
Pruritus	0/82 (0%)	0	2/37 (5.4%)	2
Rash	3/82 (3.7%)	4	2/37 (5.4%)	2
Vascular disorders
Hypotension	0/82 (0%)	0	3/37 (8.1%)	3

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.