Keywords: Huntington's Disease (HD) , Chorea , Movement Disorder , First-HD , SD-809
IRB Number: 00071315
Specialty: Neurology, Neurology, Neurology
Sub Specialties: Movement Disorders, Chorea, Huntington Disease
This is an open-label, single-arm study in which subjects with manifest HD who are receiving FDA-approved doses of tetrabenazine (TBZ) for the treatment of chorea associated with HD or have successfully completed the SD-809-C-15 efficacy study will be invited to participate. Two groups of subjects will be enrolled into this trial: Switch subjects are those who are currently receiving stable doses of tetrabenazine for treatment of chorea associated with HD and convert to SD-809 ER based on an algorithm designed to achieve comparable exposure to total (α+β)-HTBZ metabolites. Rollover subjects are those who have successfully completed Study SD-809-C-15 and are continuing on long-term SD-809 ER after a 1-week wash out period. Subjects who do not already have a legally authorized representative will undergo an independent evaluation by a qualified healthcare provider to determine their capacity to provide informed consent. Informed consent/assent will be obtained before any study procedures are performed. A Research Advance Directive (See Section 6.12) will be obtained from subjects with the ability to self consent. Subjects rolling over from the SD 809-C-15 study may have capacity assessment/informed consent/assent/research advance directive obtained up to 30 days in advance of subject’s First-HD Week 13 Visit/ARC-HD Baseline Visit. Subjects Switching from Tetrabenazine (Switch): Subjects who are currently receiving an FDA-approved dose of tetrabenazine that is providing a therapeutic benefit for chorea control may be eligible to participate in the study. Subjects in this cohort will undergo a full screening evaluation within 30 days of the Baseline assessment prior to switching to SD-809 ER (Schedule of Events A). These subjects will be converted from their TBZ regimen to an SD-809 ER regimen that is predicted to provide comparable exposure to total (α+β)-dihydrotetrabenazine (α- and β-HTBZ). Subjects will continue taking their TBZ regimen through midnight of Day 0 and then directly switch to their assigned SD 809 ER regimen the next morning. The dose of SD-809 ER may be adjusted (upward or downward) in increments of 6 mg per day (each week) until a dose level that adequately controls chorea is identified, the subject experiences a protocol defined “clinically significant” adverse event (defined as related to study medication and either a) moderate or severe in intensity or b) meets the criteria for a Serious Adverse Event [SAE]) , or the maximal allowable dose is reached. If a subject experiences a “clinically significant” AE attributable to SD-809 ER, the investigator will determine if a dose reduction or suspension is necessary. The investigator, in consultation with the subject and caregiver, will determine when an adequate level of chorea control has been achieved. Subjects will have a clinic visit at Week 1 and a telephone contact at Week 2, in order to evaluate safety and establish an optimal dose. Although subjects will enter the Long term treatment period after Week 2, dose adjustment (upward or downward) may continue through Week 4 to optimize dose level. Subjects Enrolled from the SD-809-C-15 Study (Rollover): Subjects who have successfully completed Study SD-809-C-15 may be eligible to rollover directly into this study after they complete a one week washout and the Week 13 evaluation of Study SD 809-C-15. To reduce subject burden, after obtaining capacity assessment (if necessary)/informed consent/assent and Research Advance Directive (if applicable), some data collected in the SD-809-C-15 study will be utilized in the SD-809-C-16 study and will provide some of the baseline data for SD-809-C-16 (See Schedule of Events B). In addition to assessments completed for the SD-809-C-15 Week 13 visit, evaluations required as part of the SD 809-C-16 study will be completed on the same day as the Week 13 visit. All subjects are expected to rollover to SD-809-C-16 at the Week 13 visit of SD-809-C-15. As Rollover subjects will have discontinued study drug (SD-809 ER or placebo) for 1 week at completion of the SD-809-C-15 study they will undergo titration on SD-809 ER. During titration, the investigator, in consultation with the subject and caregiver, will determine when an adequate level of chorea control has been achieved. The dose of SD 809 ER may be adjusted (upward or downward), in increments of 6 mg per day (each week), until there is adequate control of chorea, the subject experiences a protocol defined “clinically significant” adverse event (defined as related to study medication and either a) moderate or severe in intensity or b) meets the criteria for a Serious Adverse Event [SAE])1, or the maximal allowable dose is reached. If a subject experiences a “clinically significant” AE attributable to SD-809 ER, the investigator will determine if a dose reduction or suspension is necessary. Subjects will have a telephone contact at Week 1 and a clinic visit at Week 2, in order to evaluate safety and establish a dose of study drug that adequately controls chorea and is well-tolerated. Although subjects will enter the long term treatment period after Week 2, titration may continue through Week 8 to optimize dose level.
Principal Investigator: David Shprecher