An Open-Label, Long Term Safety Study of SD-809 ER in Subjects With Chorea Associated With Huntington Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 119
- 试验地点
- 38
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •Has successfully completed participation in the First-HD Study (SD-809-C-15) or
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: SD-809 (Drug)
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.
干预措施: SD-809 (Drug)
结局指标
主要结局
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
时间窗: 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.
Switch Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Dose Adjustment
时间窗: 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.
Rollover Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Titration
时间窗: 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.
Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Long Term Stable Dose Treatment
时间窗: 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.
次要结局
- Change From Baseline in Clinical Laboratory Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets) at Week 158(Baseline, Week 158)
- Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes Mean Corpuscular Volume) at Week 158(Baseline, Week 158)
- Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Alanine Aminotransferase and Alkaline Phosphatase) at Week 158(Baseline, Week 158)
- ECG Parameter Value (PR Interval, QRS Duration, QT Interval, QTcF) at Baseline and Week 8(Baseline, Week 8)
- Number of Participants With Clinically Significant Abnormalities in ECG Parameters(Baseline, Week 8)
- 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))
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) -Dysarthria Score at Week 171(Baseline, Week 171)
- Change From Baseline in Barnes Akathisia Rating Scale (BARS) Summary Score at Week 171(Baseline, Week 171)
- Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Assessment Score at Week 171(Baseline, Week 171)
- Change From Week 8 in UHDRS Motor Assessment: TMC Score at Week 171(Week 8, Week 171)
- Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes) at Week 158(Baseline, Week 158)
- Change From Baseline in Clinical Laboratory Hematology Parameter (Hematocrit) at Week 158(Baseline, Week 158)
- Change From Baseline in Clinical Laboratory Hematology Parameter (Hemoglobin) at Week 158(Baseline, Week 158)
- Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Aspartate Aminotransferase and Lactate Dehydrogenase) at Week 158(Baseline, Week 158)
- 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)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score at Week 171(Baseline, Week 171)
- Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 171(Baseline, Week 171)
- Change From Baseline in UHDRS Functional Assessment Score at Week 28(Baseline, Week 28)
- Change From Baseline in UHDRS Total Functional Capacity (TFC) Score at Week 132(Baseline, Week 132)
- Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Protein and Albumin) at Week 158(Baseline, Week 158)
- Change From Baseline in Clinical Laboratory Serum Chemistry Parameter (Creatinine Clearance) at Week 106(Baseline, Week 106)
- Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bilirubin, Creatinine, Direct Bilirubin, and Urate) at Week 158(Baseline, Week 158)
- Change From Baseline in Blood Pressure at Week 171(Baseline, Week 171)
- Change From Baseline in Heart Rate at Week 171(Baseline, Week 171)
- Change From Baseline in Respiration Rate at Week 171(Baseline, Week 171)
- Change From Baseline in Body Temperature at Week 171(Baseline, Week 171)
- Electrocardiogram (ECG) Parameter Value (Heart Rate) at Baseline and Week 8(Baseline, Week 8)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score at Week 171(Baseline, Week 171)
- 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))
- Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Behavior Score at Week 171(Baseline, Week 171)
- Change From Baseline in UHDRS Independence Scale Score at Week 28(Baseline, Week 28)
- Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 171(Baseline, Week 171)
- Change From Baseline in UHDRS Cognitive Assessment Score at Week 171(Baseline, Week 171)
- Change From Baseline in UHDRS Motor Assessment: Total Maximal Chorea (TMC) Score at Week 171(Baseline, Week 171)
- Change From Baseline in UHDRS Motor Assessment: Total Motor Score (TMS) at Week 171(Baseline, Week 171)
- Change From Week 8 in UHDRS Motor Assessment: TMS at Week 171(Week 8, Week 171)