First Time Use of SD-809 in Huntington Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether SD-809 tablets are effective in the treatment of chorea associated with Huntington's Disease.

Detailed Description
-----------------
This is a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety and tolerability of SD-809 for the treatment of chorea associated with Huntington's Disease. Approximately 90 subjects will be randomized (1:1) into the study, with approximately 45 subjects receiving SD-809 and 45 subjects receiving placebo. The study will be conducted at approximately 30 centers in the U.S. and Canada.

Official Title
-----------------
A Randomized Double-Blind, Placebo-Controlled Study of SD-809 Extended Release for the Treatment of Chorea Associated With Huntington Disease

Conditions
-----------------
Chorea

Intervention / Treatment
-----------------
* Drug: SD-809
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is at least 18 years of age or the age of majority (whichever is older) at Screening. Subject has been diagnosed with manifest HD Subject is able to swallow study medication whole. Female subjects of childbearing potential agree to use an acceptable method of contraception from screening through study completion. The subject has a reliable caregiver who interacts with the patient on a daily basis, oversees study drug administration, assures attendance at study visits and participates in evaluations, as required. Subject is able to ambulate without assistance for at least 20 yards (Note: The use of assistive devices (i.e., walker, cane) is permitted during ambulation). Exclusion Criteria: Subject has a serious untreated or under-treated psychiatric illness, such as depression, at Screening or Baseline. Subject has active suicidal ideation at Screening or Baseline. Subject has history of suicidal behavior at Screening or Baseline: Subject has evidence for depression at Screening or Baseline. Subject has an unstable or serious medical or psychiatric illness at Screening or Baseline. Subject has been recently exposed to tetrabenazine. Subject 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 Subject has significantly impaired swallowing function at Screening. Subject has significantly impaired speaking at Screening. Subject requires treatment with drugs known to prolong the QT interval. Subject has a prolonged QT interval on 12-lead ECG at Screening. Subject has evidence of hepatic impairment at Screening. Subject has evidence of significant renal impairment at Screening. Subject has known allergy to any of the components of study medication. Subject has participated in an investigational drug or device trial within 30 days (or 5 drug half-lives) of Screening, whichever is longer. Subject is pregnant or breast-feeding at Screening or Baseline. Subject acknowledges present use of illicit drugs at Screening. Subject has a history of alcohol or substance abuse in the previous 12 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SD-809 ER Tablets<br>SD-809 ER tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white). All are administered three times a day, with the 6 mg final dose is placebo. | Drug: SD-809<br>* SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).<br>* Other names: deutetrabenazine;Drug: Placebo<br>* Placebo tablets are identical in appearance to SD-809 tablets.<br>|
| Experimental: SD-809 Tablets<br>SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white). All are administered three times a day, with the 6 mg final dose is placebo. | Drug: SD-809<br>* SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).<br>* Other names: deutetrabenazine;Drug: Placebo<br>* Placebo tablets are identical in appearance to SD-809 tablets.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12 | Total TMC score is a sum of chorea scores which range 0-28, with a decrease indicating improvement in chorea | Screening, Day 0, Weeks 9, 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC) | A treatment success is defined as Much or Very Much Improved at the Week 12 visit. The PGIC is a 7-point Likert Scale, ranging from very much worse to very much improved | 12 weeks | 
| Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC) | A treatment success is defined as Much or Very Much Improved at the Week 12 visit. The PGIC is a 7-point Likert Scale, ranging from very much worse to very much improved. The clinician was asked to comment about the subject. | 12 weeks | 
| Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12 | Change in the Short Form 36 Health Survey (SF-36) physical functioning score (based on items 3a to 3j) from Baseline to Week 12. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | Baseline, 12 weeks | 
| Change in Berg Balance Test (BBT) | The Berg Balance Test (BBT) is a 14-item assessment of sitting, standing, transferring, and turning. Each task ranging from standing up from a sitting position, to standing on one foot each task is given a score of zero (unable) to four (independent), and the final measure is the sum of all of the scores.The scale range, which is 0-56, with higher scores indicating better balance/lower fall risk. | Baseline, 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Huntington disease, Chorea, Tetrabenazine