Chorea
Conditions
Keywords
Huntington disease, Chorea, Tetrabenazine
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.
Interventions
DRUGSD-809
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).
DRUGPlacebo
Placebo tablets are identical in appearance to SD-809 tablets.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12 | Screening, Day 0, Weeks 9, 12 | Total TMC score is a sum of chorea scores which range 0-28, with a decrease indicating improvement in chorea |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC) | 12 weeks | 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 |
| Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC) | 12 weeks | 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. |
| Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12 | Baseline, 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. 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. |
| Change in Berg Balance Test (BBT) | Baseline, 12 weeks | 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. |
Countries
Australia, Canada, United States
Participant flow
Recruitment details
A total of 90 subjects were randomized 1:1 to receive either SD-809 or placebo. All subjects were assessed for capacity to provide informed consent and written informed consent was obtained appropriately
Participants by arm
| Arm | Count |
|---|---|
| SD-809 Tablets SD-809: 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). | 45 |
| SD-809 Placebo Placebo: Placebo tablets are identical in appearance to SD-809 tablets. | 45 |
| Total | 90 |
Baseline characteristics
| Characteristic | Total | SD-809 Placebo | SD-809 Tablets |
|---|---|---|---|
| Age, Customized SD-809 | 53.7 participants STANDARD_DEVIATION 11.98 | 52.1 participants STANDARD_DEVIATION 13.36 | 55.4 participants STANDARD_DEVIATION 10.32 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 83 Participants | 38 Participants | 45 Participants |
| Sex: Female, Male Female | 40 Participants | 17 Participants | 23 Participants |
| Sex: Female, Male Male | 50 Participants | 28 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 45 | 18 / 45 |
| serious Total, serious adverse events | 1 / 45 | 1 / 45 |
Outcome results
Primary
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
Time frame: Screening, Day 0, Weeks 9, 12
Population: The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one postbaseline assessment. For subjects who missed both Week 9 or Week 12 scores, the last available assessment was used
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SD-809 Tablets | Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12 | -4.42 Units on a scale | Standard Deviation 2.953 |
| SD-809 Placebo | Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12 | -1.93 Units on a scale | Standard Deviation 2.666 |
p-value: <0.000195% CI: [-3.69, -1.29]ANCOVA
Secondary
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.
Time frame: Baseline, 12 weeks
Population: The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one postbaseline assessment. For subjects with missing value at Week 12, the last available assessment was used
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SD-809 Tablets | Change in Berg Balance Test (BBT) | 2.2 units on a scale | Standard Deviation 3.47 |
| SD-809 Placebo | Change in Berg Balance Test (BBT) | 1.3 units on a scale | Standard Deviation 4.04 |
p-value: 0.141595% CI: [-0.3, 2.3]Mixed Models Analysis
Secondary
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.
Time frame: Baseline, 12 weeks
Population: The modified intent to treat (mITT) population will include all subjects in the ITT population who were randomized to treatment and received study drug. For subjects with missing value at Week 12, the last available assessment was used
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SD-809 Tablets | Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12 | 0.74 units on a scale | Standard Deviation 9.773 |
| SD-809 Placebo | Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12 | -3.61 units on a scale | Standard Deviation 9.669 |
p-value: 0.030895% CI: [0.41, 8.27]Mixed Models Analysis
Secondary
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
Time frame: 12 weeks
Population: The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one post baseline assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SD-809 Tablets | Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC) | 23 Participants |
| SD-809 Placebo | Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC) | 9 Participants |
p-value: 0.00295% CI: [12.4, 49.8]Difference of proportions
Secondary
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.
Time frame: 12 weeks
Population: The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one post-baseline assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SD-809 Tablets | Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC) | 19 Participants |
| SD-809 Placebo | Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC) | 6 Participants |
p-value: 0.002295% CI: [11.4, 46.4]Difference of proportions