Trial Outcomes & Findings for Addressing Involuntary Movements in Tardive Dyskinesia (NCT NCT02291861)
NCT ID: NCT02291861
Last Updated: 2021-11-09
Results Overview
AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. AIMS is composed of 12 clinician-administered and scored items. The exam was digitally video recorded using a standard protocol, and independently reviewed by blinded central raters who were experts in movement disorders. This outcome sums items 1 through 7 which cover orofacial movements, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. MMRM with treatment group, visit, treatment group-by-visit interaction, and baseline use of dopamine receptor antagonist (DRAs) as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
COMPLETED
PHASE3
298 participants
Day 0 (Baseline), Weeks 2, 4, 8 and 12
2021-11-09
Participant Flow
This study was performed at 75 study centers (38 in the US, 19 in Poland, 7 in Hungary, 6 in the Czech Republic, 3 in Slovakia, and 2 in Germany) by 75 investigators; 298 patients were enrolled.
Participants were randomly assigned in a 1:1:1:1 ratio to receive 1 of 3 fixed-dose regimens of SD-809 (deutetrabenazine) or placebo following a screening period.
Participant milestones
| Measure |
Placebo
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
74
|
75
|
74
|
75
|
|
Overall Study
Safety Population
|
72
|
74
|
73
|
74
|
|
Overall Study
Modified Intent to Treat Pop (mITT)
|
58
|
60
|
49
|
55
|
|
Overall Study
COMPLETED
|
67
|
67
|
65
|
65
|
|
Overall Study
NOT COMPLETED
|
7
|
8
|
9
|
10
|
Reasons for withdrawal
| Measure |
Placebo
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
4
|
1
|
2
|
|
Overall Study
Death
|
0
|
0
|
1
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
1
|
4
|
|
Overall Study
Noncompliance
|
1
|
1
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
4
|
0
|
|
Overall Study
Other
|
0
|
0
|
0
|
1
|
Baseline Characteristics
One participant in the SD-809 12 mg/day group was missing a baseline mCDQ-24 total score.
Baseline characteristics by cohort
| Measure |
Placebo
n=72 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=74 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=73 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=74 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
Total
n=293 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
54.6 years
STANDARD_DEVIATION 12.06 • n=72 Participants
|
57.0 years
STANDARD_DEVIATION 9.95 • n=74 Participants
|
55.6 years
STANDARD_DEVIATION 11.34 • n=73 Participants
|
58.3 years
STANDARD_DEVIATION 11.55 • n=74 Participants
|
56.4 years
STANDARD_DEVIATION 11.27 • n=293 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=72 Participants
|
42 Participants
n=74 Participants
|
41 Participants
n=73 Participants
|
42 Participants
n=74 Participants
|
162 Participants
n=293 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=72 Participants
|
32 Participants
n=74 Participants
|
32 Participants
n=73 Participants
|
32 Participants
n=74 Participants
|
131 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=72 Participants
|
1 Participants
n=74 Participants
|
0 Participants
n=73 Participants
|
2 Participants
n=74 Participants
|
4 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=72 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=73 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
12 Participants
n=72 Participants
|
15 Participants
n=74 Participants
|
19 Participants
n=73 Participants
|
10 Participants
n=74 Participants
|
56 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
0 Participants
n=72 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=73 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
White
|
59 Participants
n=72 Participants
|
58 Participants
n=74 Participants
|
54 Participants
n=73 Participants
|
61 Participants
n=74 Participants
|
232 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=72 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=73 Participants
|
1 Participants
n=74 Participants
|
1 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
Hispanic or latino
|
7 Participants
n=72 Participants
|
6 Participants
n=74 Participants
|
3 Participants
n=73 Participants
|
7 Participants
n=74 Participants
|
23 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
Not hispanic or latino
|
64 Participants
n=72 Participants
|
64 Participants
n=74 Participants
|
69 Participants
n=73 Participants
|
65 Participants
n=74 Participants
|
262 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
Not reported
|
0 Participants
n=72 Participants
|
3 Participants
n=74 Participants
|
1 Participants
n=73 Participants
|
1 Participants
n=74 Participants
|
5 Participants
n=293 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
1 Participants
n=72 Participants
|
1 Participants
n=74 Participants
|
0 Participants
n=73 Participants
|
1 Participants
n=74 Participants
|
3 Participants
n=293 Participants
|
|
Weight
|
82.8 kg
STANDARD_DEVIATION 18.51 • n=72 Participants
|
80.8 kg
STANDARD_DEVIATION 21.00 • n=74 Participants
|
86.8 kg
STANDARD_DEVIATION 18.79 • n=73 Participants
|
78.5 kg
STANDARD_DEVIATION 17.56 • n=74 Participants
|
82.2 kg
STANDARD_DEVIATION 19.16 • n=293 Participants
|
|
Height
|
168.3 cm
STANDARD_DEVIATION 9.25 • n=72 Participants
|
167.7 cm
STANDARD_DEVIATION 10.68 • n=74 Participants
|
168.7 cm
STANDARD_DEVIATION 9.39 • n=73 Participants
|
167.6 cm
STANDARD_DEVIATION 10.55 • n=74 Participants
|
168.1 cm
STANDARD_DEVIATION 9.96 • n=293 Participants
|
|
Body Mass Index
|
29.18 kg/m^2
STANDARD_DEVIATION 6.128 • n=72 Participants
|
28.69 kg/m^2
STANDARD_DEVIATION 6.814 • n=74 Participants
|
30.64 kg/m^2
STANDARD_DEVIATION 7.021 • n=73 Participants
|
27.99 kg/m^2
STANDARD_DEVIATION 6.178 • n=74 Participants
|
29.12 kg/m^2
STANDARD_DEVIATION 6.587 • n=293 Participants
|
|
Education Level
<= 12 years
|
40 Participants
n=72 Participants
|
44 Participants
n=74 Participants
|
44 Participants
n=73 Participants
|
39 Participants
n=74 Participants
|
167 Participants
n=293 Participants
|
|
Education Level
> 12 years
|
32 Participants
n=72 Participants
|
30 Participants
n=74 Participants
|
29 Participants
n=73 Participants
|
35 Participants
n=74 Participants
|
126 Participants
n=293 Participants
|
|
Time Since Tardive Dyskinesia (TD) Diagnosis
|
6.03 years
STANDARD_DEVIATION 5.353 • n=72 Participants
|
5.49 years
STANDARD_DEVIATION 5.426 • n=74 Participants
|
4.98 years
STANDARD_DEVIATION 6.034 • n=73 Participants
|
5.89 years
STANDARD_DEVIATION 5.342 • n=74 Participants
|
5.60 years
STANDARD_DEVIATION 5.532 • n=293 Participants
|
|
Total Motor Abnormal Involuntary Movement Scale (AIMS) Score
|
8.5 units on a scale
STANDARD_DEVIATION 3.28 • n=72 Participants
|
8.6 units on a scale
STANDARD_DEVIATION 3.13 • n=74 Participants
|
7.7 units on a scale
STANDARD_DEVIATION 3.51 • n=73 Participants
|
8.6 units on a scale
STANDARD_DEVIATION 3.84 • n=74 Participants
|
8.4 units on a scale
STANDARD_DEVIATION 3.46 • n=293 Participants
|
|
Modified Craniocervical Dystonia Questionnaire (mCDQ-24)
|
40.5 units on a scale
STANDARD_DEVIATION 19.88 • n=72 Participants • One participant in the SD-809 12 mg/day group was missing a baseline mCDQ-24 total score.
|
37.2 units on a scale
STANDARD_DEVIATION 20.15 • n=73 Participants • One participant in the SD-809 12 mg/day group was missing a baseline mCDQ-24 total score.
|
34.4 units on a scale
STANDARD_DEVIATION 19.59 • n=73 Participants • One participant in the SD-809 12 mg/day group was missing a baseline mCDQ-24 total score.
|
34.9 units on a scale
STANDARD_DEVIATION 18.34 • n=74 Participants • One participant in the SD-809 12 mg/day group was missing a baseline mCDQ-24 total score.
|
36.7 units on a scale
STANDARD_DEVIATION 19.55 • n=292 Participants • One participant in the SD-809 12 mg/day group was missing a baseline mCDQ-24 total score.
|
|
Baseline Use of a Dopamine Receptor Antagonist (DRA)
Yes
|
56 Participants
n=72 Participants
|
56 Participants
n=74 Participants
|
57 Participants
n=73 Participants
|
53 Participants
n=74 Participants
|
222 Participants
n=293 Participants
|
|
Baseline Use of a Dopamine Receptor Antagonist (DRA)
No
|
16 Participants
n=72 Participants
|
18 Participants
n=74 Participants
|
16 Participants
n=73 Participants
|
21 Participants
n=74 Participants
|
71 Participants
n=293 Participants
|
PRIMARY outcome
Timeframe: Day 0 (Baseline), Weeks 2, 4, 8 and 12Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. For this outcome, participants with baseline readings and during-study readings through Week 12 are included.
AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. AIMS is composed of 12 clinician-administered and scored items. The exam was digitally video recorded using a standard protocol, and independently reviewed by blinded central raters who were experts in movement disorders. This outcome sums items 1 through 7 which cover orofacial movements, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. MMRM with treatment group, visit, treatment group-by-visit interaction, and baseline use of dopamine receptor antagonist (DRAs) as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
Outcome measures
| Measure |
Placebo
n=56 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=53 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=45 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=52 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM)
|
-1.4 units on a scale
Standard Error 0.41
|
-2.1 units on a scale
Standard Error 0.42
|
-3.2 units on a scale
Standard Error 0.45
|
-3.3 units on a scale
Standard Error 0.42
|
SECONDARY outcome
Timeframe: Week 12Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment.
The CGIC is a single-item questionnaire that asks the investigator to assess a patient's TD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as "much improved" or "very much improved" at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not "much improved" or "very much improved" at the week 12 visit, were considered treatment failures. The success 95% confidence interval (CI) was calculated with the Wilson (score) confidence limits.
Outcome measures
| Measure |
Placebo
n=58 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=60 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=49 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=55 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)
|
26 percentage of participants
Interval 16.3 to 38.4
|
28 percentage of participants
Interval 18.5 to 40.8
|
49 percentage of participants
Interval 35.6 to 62.5
|
44 percentage of participants
Interval 31.4 to 56.7
|
SECONDARY outcome
Timeframe: Day 0 (Baseline), Week 12Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. One SD-809 12 mg/day participant was missing a baseline mCDQ-24.
The CDQ-24 is a disease-specific quality of life questionnaire developed for use in patients with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ 24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains are evaluated in the mCDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 - 96. Negative change from baseline scores indicate improvement. For patients with missing data at week 12, the baseline or last available value was used as the week 12 value.
Outcome measures
| Measure |
Placebo
n=58 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=59 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=49 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=55 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score From Baseline to Week 12
|
-7.1 units on a scale
Standard Error 2.06
|
-5.8 units on a scale
Standard Error 2.03
|
-10.2 units on a scale
Standard Error 2.21
|
-10.7 units on a scale
Standard Error 2.04
|
SECONDARY outcome
Timeframe: Week 12Population: mITT population
The PGIC is a single-item questionnaire that asks the patient to assess their TD symptoms at specific visits after initiating therapy. The PGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as "much improved" or "very much improved" at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not "much improved" or "very much improved" at the week 12 visit, were considered treatment failures. The success 95% CI was calculated with the Wilson (score) confidence limits.
Outcome measures
| Measure |
Placebo
n=58 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=60 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=49 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=55 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)
|
31 percentage of participants
Interval 20.6 to 43.8
|
23 percentage of participants
Interval 14.4 to 35.4
|
45 percentage of participants
Interval 31.9 to 58.7
|
40 percentage of participants
Interval 28.1 to 53.2
|
SECONDARY outcome
Timeframe: Day 0 (Baseline), Week 12Population: mITT population of participants. Participants with missing Week 12 data were considered non-responders.
Responders who had a 50% or greater improvement in total motor modified AIMS at Week 12 as compared to baseline were reported as a percentage of participants with an outcome at Week 12. The responder 95% CI is calculated with the Wilson (score) confidence limits. AIMS is an assessment tool used to detect and follow the severity of TD over time. AIMS is composed of 12 clinician-administered and scored items. The exam was digitally video recorded using a standard protocol, and independently reviewed by blinded central raters who were experts in movement disorders. This outcome sums items 1 through 7 which cover orofacial movements, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement.
Outcome measures
| Measure |
Placebo
n=58 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=60 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=49 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=55 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants Who Had a 50% or Greater Reduction in Total Motor Abnormal Involuntary Movement Scale (AIMS) From Baseline to Week 12
|
12 percentage of participants
Interval 6.0 to 22.9
|
13 percentage of participants
Interval 6.9 to 24.2
|
35 percentage of participants
Interval 22.9 to 48.7
|
33 percentage of participants
Interval 21.8 to 45.9
|
SECONDARY outcome
Timeframe: Day 0 (Baseline), Weeks 2, 4, 8 and 12Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. For this outcome, participants with baseline readings and during-study readings through Week 12 are included.
AIMS is an assessment tool used to detect and follow the severity of TD over time. AIMS is composed of 12 clinician-administered and scored items. The exam was digitally video recorded using a standard protocol, and independently reviewed by blinded central raters who were experts in movement disorders. This outcome sums items 1 through 7 which cover orofacial movements, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. MMRM with treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
Outcome measures
| Measure |
Placebo
n=56 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=53 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=45 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=52 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Percent Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model for Repeated Measures (MMRM)
|
-11.6 percentage of baseline
Standard Error 4.32
|
-20.0 percentage of baseline
Standard Error 4.34
|
-31.9 percentage of baseline
Standard Error 4.73
|
-33.1 percentage of baseline
Standard Error 4.38
|
SECONDARY outcome
Timeframe: Day 0 (Baseline), Week 12Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment.
AIMS is an assessment tool used to detect and follow the severity of TD over time, composed of 12 clinician-administered and scored items. The exam was digitally video recorded using a standard protocol, and independently reviewed by blinded central raters who were experts in movement disorders. This outcome sums items 1 through 7 which cover orofacial movements, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. Participants with missing data are classified as non-responders. The responder 95% CI is calculated with the Wilson (score) confidence limits. If any of the expected cell counts are \< 5, exact Clopper Pearson limits are presented. Data report the percentage of participants who responded to the percentage improvement indicated in each row.
Outcome measures
| Measure |
Placebo
n=58 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=60 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=49 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=55 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
40% Improvement
|
16 percentage of participants
Interval 8.4 to 26.9
|
23 percentage of participants
Interval 14.4 to 35.4
|
45 percentage of participants
Interval 31.9 to 58.7
|
40 percentage of participants
Interval 28.1 to 53.2
|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
90% Improvement
|
2 percentage of participants
Interval 0.0 to 9.2
|
0 percentage of participants
Interval 0.0 to 6.0
|
0 percentage of participants
Interval 0.0 to 7.3
|
5 percentage of participants
Interval 1.1 to 15.1
|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
10% Improvement
|
50 percentage of participants
Interval 37.5 to 62.5
|
62 percentage of participants
Interval 49.0 to 72.9
|
67 percentage of participants
Interval 53.4 to 78.8
|
71 percentage of participants
Interval 57.9 to 81.2
|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
20% Improvement
|
40 percentage of participants
Interval 28.1 to 52.5
|
47 percentage of participants
Interval 34.6 to 59.1
|
59 percentage of participants
Interval 45.2 to 71.8
|
60 percentage of participants
Interval 46.8 to 71.9
|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
30% Improvement
|
31 percentage of participants
Interval 20.6 to 43.8
|
32 percentage of participants
Interval 21.3 to 44.2
|
49 percentage of participants
Interval 35.6 to 62.5
|
49 percentage of participants
Interval 36.4 to 61.9
|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
50% Improvement
|
12 percentage of participants
Interval 6.0 to 22.9
|
13 percentage of participants
Interval 6.9 to 24.2
|
35 percentage of participants
Interval 22.9 to 48.7
|
33 percentage of participants
Interval 21.8 to 45.9
|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
60% Improvement
|
5 percentage of participants
Interval 1.8 to 14.1
|
7 percentage of participants
Interval 2.6 to 15.9
|
20 percentage of participants
Interval 11.5 to 33.6
|
18 percentage of participants
Interval 10.2 to 30.3
|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
70% Improvement
|
2 percentage of participants
Interval 0.0 to 9.2
|
3 percentage of participants
Interval 0.4 to 11.5
|
12 percentage of participants
Interval 4.6 to 24.8
|
16 percentage of participants
Interval 7.8 to 28.8
|
|
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
80% Improvement
|
2 percentage of participants
Interval 0.0 to 9.2
|
2 percentage of participants
Interval 0.0 to 8.9
|
2 percentage of participants
Interval 0.1 to 10.9
|
13 percentage of participants
Interval 5.3 to 24.5
|
SECONDARY outcome
Timeframe: Day 1 to Week 12Population: The Safety Population was a subset of randomized participants and included all patients who were administered study drug (N=293).
An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator and includes possibly, probably and definitely related categories. Serious AEs (SAE) include death, a life-threatening adverse event, 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 patient and required medical intervention to prevent the previously listed serious outcomes.
Outcome measures
| Measure |
Placebo
n=72 Participants
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=74 Participants
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=73 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=74 Participants
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Participants With Adverse Events During the Overall Treatment Period
Overall Treatment Period: any AE
|
34 Participants
|
36 Participants
|
32 Participants
|
38 Participants
|
|
Participants With Adverse Events During the Overall Treatment Period
Overall Treatment Period: SAE
|
4 Participants
|
2 Participants
|
6 Participants
|
4 Participants
|
|
Participants With Adverse Events During the Overall Treatment Period
Overall Treatment Period: Severe AE
|
2 Participants
|
2 Participants
|
4 Participants
|
1 Participants
|
|
Participants With Adverse Events During the Overall Treatment Period
Overall Treatment Period: treatment-related AE
|
19 Participants
|
13 Participants
|
11 Participants
|
18 Participants
|
|
Participants With Adverse Events During the Overall Treatment Period
Dose reduction because of AE
|
0 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
|
Participants With Adverse Events During the Overall Treatment Period
Dose suspension because of AE
|
2 Participants
|
3 Participants
|
1 Participants
|
1 Participants
|
|
Participants With Adverse Events During the Overall Treatment Period
Withdrawn from study because of AE
|
2 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
Adverse Events
Placebo
SD-809 12 mg/Day
SD-809 24 mg/Day
SD-809 36 mg/Day
Serious adverse events
| Measure |
Placebo
n=72 participants at risk
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=74 participants at risk
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=73 participants at risk
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=74 participants at risk
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Abdominal pain
|
1.4%
1/72 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Pancreatic mass
|
1.4%
1/72 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
General disorders
Alcohol interaction
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
|
General disorders
Sudden cardiac death
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
1.4%
1/73 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Infections and infestations
Appendicitis
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
1.4%
1/73 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Infections and infestations
Cellulitis
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
1.4%
1/73 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Infections and infestations
Pneumonia
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
1.4%
1/73 • Number of events 1 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Face injury
|
0.00%
0/72 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Head injury
|
1.4%
1/72 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Skeletal injury
|
0.00%
0/72 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma metastatic
|
1.4%
1/72 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Nervous system disorders
Psychomotor hyperactivity
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
|
Psychiatric disorders
Bipolar disorder
|
1.4%
1/72 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Psychiatric disorders
Depression
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
1.4%
1/73 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/72 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/73 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/72 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
1.4%
1/73 • Number of events 1 • Day 1 to Week 12
|
0.00%
0/74 • Day 1 to Week 12
|
Other adverse events
| Measure |
Placebo
n=72 participants at risk
Placebo tablets taken twice daily for 12 weeks.
|
SD-809 12 mg/Day
n=74 participants at risk
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
|
SD-809 24 mg/Day
n=73 participants at risk
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.
|
SD-809 36 mg/Day
n=74 participants at risk
SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.8%
2/72 • Number of events 2 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
4.1%
3/73 • Number of events 4 • Day 1 to Week 12
|
6.8%
5/74 • Number of events 6 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Nausea
|
9.7%
7/72 • Number of events 8 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
1.4%
1/73 • Number of events 1 • Day 1 to Week 12
|
1.4%
1/74 • Number of events 1 • Day 1 to Week 12
|
|
Infections and infestations
Nasopharyngitis
|
1.4%
1/72 • Number of events 1 • Day 1 to Week 12
|
5.4%
4/74 • Number of events 4 • Day 1 to Week 12
|
4.1%
3/73 • Number of events 3 • Day 1 to Week 12
|
2.7%
2/74 • Number of events 2 • Day 1 to Week 12
|
|
Nervous system disorders
Headache
|
5.6%
4/72 • Number of events 4 • Day 1 to Week 12
|
6.8%
5/74 • Number of events 7 • Day 1 to Week 12
|
2.7%
2/73 • Number of events 3 • Day 1 to Week 12
|
6.8%
5/74 • Number of events 5 • Day 1 to Week 12
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data
- Publication restrictions are in place
Restriction type: OTHER