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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01897896




Registration number
NCT01897896
Ethics application status
Date submitted
14/06/2013
Date registered
12/07/2013
Date last updated
16/04/2019

Titles & IDs
Public title
Alternatives for Reducing Chorea in Huntington Disease
Scientific title
An Open-Label, Long Term Safety Study of SD-809 ER in Subjects With Chorea Associated With Huntington Disease
Secondary ID [1] 0 0
SD-809-C-16
Universal Trial Number (UTN)
Trial acronym
ARC-HD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chorea Associated With Huntington Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SD-809

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.

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.


Treatment: Drugs: SD-809
SD-809 tablets will be provided in dose strengths of 6, 9 and 12 mg.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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 - 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.
Timepoint [1] 0 0
Baseline to follow-up visit (up to approximately 3 years 9 months)
Primary outcome [2] 0 0
Rollover Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Titration - 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.
Timepoint [2] 0 0
Day 1 to end of Week 8
Primary outcome [3] 0 0
Switch Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Dose Adjustment - 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.
Timepoint [3] 0 0
Day 1 to end of Week 4
Primary outcome [4] 0 0
Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Long Term Stable Dose Treatment - 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.
Timepoint [4] 0 0
Week 8 to follow-up visit (up to approximately 3 years 9 months)
Secondary outcome [1] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets) at 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.
Timepoint [1] 0 0
Baseline, Week 158
Secondary outcome [2] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes Mean Corpuscular Volume) at 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.
Timepoint [2] 0 0
Baseline, Week 158
Secondary outcome [3] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes) at 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.
Timepoint [3] 0 0
Baseline, Week 158
Secondary outcome [4] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameter (Hematocrit) at 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.
Timepoint [4] 0 0
Baseline, Week 158
Secondary outcome [5] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameter (Hemoglobin) at 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.
Timepoint [5] 0 0
Baseline, Week 158
Secondary outcome [6] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Alanine Aminotransferase and Alkaline Phosphatase) at 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.
Timepoint [6] 0 0
Baseline, Week 158
Secondary outcome [7] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Aspartate Aminotransferase and Lactate Dehydrogenase) at 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.
Timepoint [7] 0 0
Baseline, Week 158
Secondary outcome [8] 0 0
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 - 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.
Timepoint [8] 0 0
Baseline, Week 158
Secondary outcome [9] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Protein and Albumin) at 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.
Timepoint [9] 0 0
Baseline, Week 158
Secondary outcome [10] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameter (Creatinine Clearance) at 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.
Timepoint [10] 0 0
Baseline, Week 106
Secondary outcome [11] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bilirubin, Creatinine, Direct Bilirubin, and Urate) at 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.
Timepoint [11] 0 0
Baseline, Week 158
Secondary outcome [12] 0 0
Change From Baseline in Blood Pressure at 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.
Timepoint [12] 0 0
Baseline, Week 171
Secondary outcome [13] 0 0
Change From Baseline in Heart Rate at 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.
Timepoint [13] 0 0
Baseline, Week 171
Secondary outcome [14] 0 0
Change From Baseline in Respiration Rate at Week 171 - Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.
Timepoint [14] 0 0
Baseline, Week 171
Secondary outcome [15] 0 0
Change From Baseline in Body Temperature at Week 171 - Observed value at baseline and observed value at Week 171 were used to calculate the change from baseline value at Week 171.
Timepoint [15] 0 0
Baseline, Week 171
Secondary outcome [16] 0 0
Electrocardiogram (ECG) Parameter Value (Heart Rate) at Baseline and 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.
Timepoint [16] 0 0
Baseline, Week 8
Secondary outcome [17] 0 0
ECG Parameter Value (PR Interval, QRS Duration, QT Interval, QTcF) at Baseline and 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.
Timepoint [17] 0 0
Baseline, Week 8
Secondary outcome [18] 0 0
Number of Participants With Clinically Significant Abnormalities in ECG Parameters - ECG parameters included heart rate, PR interval, QRS duration, QT interval and QTcF. Clinical significance was as as per Investigator's discretion.
Timepoint [18] 0 0
Baseline, Week 8
Secondary outcome [19] 0 0
Duration of Time to Achieve a Stable Dose of SD-809 ER - 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.
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) -Dysarthria Score at 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.
Timepoint [20] 0 0
Baseline, Week 171
Secondary outcome [21] 0 0
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Summary Score at 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.
Timepoint [21] 0 0
Baseline, Week 171
Secondary outcome [22] 0 0
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Assessment Score at 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.
Timepoint [22] 0 0
Baseline, Week 171
Secondary outcome [23] 0 0
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score at 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.
Timepoint [23] 0 0
Baseline, Week 171
Secondary outcome [24] 0 0
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score at 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.
Timepoint [24] 0 0
Baseline, Week 171
Secondary outcome [25] 0 0
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at 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.
Timepoint [25] 0 0
Baseline, Week 171
Secondary outcome [26] 0 0
Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) - 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.
Timepoint [26] 0 0
Baseline up to 1-week follow-up visit (up to approximately 3 years 9 months)
Secondary outcome [27] 0 0
Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at 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.
Timepoint [27] 0 0
Baseline, Week 171
Secondary outcome [28] 0 0
Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Behavior Score at 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.
Timepoint [28] 0 0
Baseline, Week 171
Secondary outcome [29] 0 0
Change From Baseline in UHDRS Functional Assessment Score at 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.
Timepoint [29] 0 0
Baseline, Week 28
Secondary outcome [30] 0 0
Change From Baseline in UHDRS Independence Scale Score at 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.
Timepoint [30] 0 0
Baseline, Week 28
Secondary outcome [31] 0 0
Change From Baseline in UHDRS Total Functional Capacity (TFC) Score at 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.
Timepoint [31] 0 0
Baseline, Week 132
Secondary outcome [32] 0 0
Change From Baseline in UHDRS Cognitive Assessment Score at 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.
Timepoint [32] 0 0
Baseline, Week 171
Secondary outcome [33] 0 0
Change From Baseline in UHDRS Motor Assessment: Total Maximal Chorea (TMC) Score at 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.
Timepoint [33] 0 0
Baseline, Week 171
Secondary outcome [34] 0 0
Change From Week 8 in UHDRS Motor Assessment: TMC Score at 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.
Timepoint [34] 0 0
Week 8, Week 171
Secondary outcome [35] 0 0
Change From Baseline in UHDRS Motor Assessment: Total Motor Score (TMS) at 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.
Timepoint [35] 0 0
Baseline, Week 171
Secondary outcome [36] 0 0
Change From Week 8 in UHDRS Motor Assessment: TMS at 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.
Timepoint [36] 0 0
Week 8, Week 171

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Teva Investigational Site 054 - Sydney
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oklahoma
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Utah
Country [24] 0 0
United States of America
State/province [24] 0 0
Vermont
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
Canada
State/province [26] 0 0
Montreal
Country [27] 0 0
Canada
State/province [27] 0 0
Ottawa
Country [28] 0 0
Canada
State/province [28] 0 0
Toronto

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Auspex Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01897896
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Teva Medical Expert, MD
Address 0 0
Teva Pharmaceuticals USA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications