Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Aim to Reduce Movements in Tardive Dyskinesia (ARM-TD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02195700
Recruitment Status : Completed
First Posted : July 21, 2014
Results First Posted : March 20, 2018
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Auspex Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Tardive Dyskinesia
Interventions Drug: SD-809
Drug: Placebo
Enrollment 117
Recruitment Details  
Pre-assignment Details 202 patients were screened and gave informed consent to enter the study. 85 were either ineligible for entry into the study or declined study participation. The most common reason for ineligibility (49 patients) was insufficient TD severity as assessed with Abnormal Involuntary Movement Scale (AIMS). 117 patients were randomized.
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Period Title: Overall Study
Started 58 59
Safety and ITT Populations 58 59
Modified ITT Population 56 [1] 57 [1]
Maintenance Period 53 54
Completed 52 52
Not Completed 6 7
Reason Not Completed
Protocol Violation             0             2
Noncompliance             1             0
Adverse Event             1             2
Withdrawal by Subject             3             2
Lost to Follow-up             1             1
[1]
ITT who received study drug and >=1 centrally read post-baseline AIMS from weeks 2, 4, 6, 9, or 12
Arm/Group Title SD-809 Placebo Total
Hide Arm/Group Description

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Total of all reporting groups
Overall Number of Baseline Participants 58 59 117
Hide Baseline Analysis Population Description
ITT population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants 59 participants 117 participants
55.9  (9.82) 53.3  (10.64) 54.6  (10.28)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 59 participants 117 participants
Female
29
  50.0%
32
  54.2%
61
  52.1%
Male
29
  50.0%
27
  45.8%
56
  47.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 59 participants 117 participants
Hispanic or Latino
4
   6.9%
11
  18.6%
15
  12.8%
Not Hispanic or Latino
53
  91.4%
47
  79.7%
100
  85.5%
Unknown or Not Reported
1
   1.7%
1
   1.7%
2
   1.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 59 participants 117 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   3.4%
1
   1.7%
3
   2.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
19
  32.8%
14
  23.7%
33
  28.2%
White
37
  63.8%
44
  74.6%
81
  69.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Education Level  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 59 participants 117 participants
=12 years or fewer of formal education
30
  51.7%
30
  50.8%
60
  51.3%
>12 years of formal education
28
  48.3%
29
  49.2%
57
  48.7%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 58 participants 59 participants 117 participants
86.94  (24.081) 84.95  (20.975) 85.94  (22.493)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 58 participants 59 participants 117 participants
169.23  (11.462) 169.72  (10.098) 169.48  (10.752)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 58 participants 59 participants 117 participants
30.35  (7.926) 29.45  (6.958) 29.89  (7.435)
Using a Dopamine Receptor Antagonist (DRA)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 59 participants 117 participants
Yes
45
  77.6%
49
  83.1%
94
  80.3%
No
13
  22.4%
10
  16.9%
23
  19.7%
[1]
Measure Description: The randomization was stratified by baseline use of DRA (currently taking versus not currently taking a DRA).
Duration of tardive dyskinesia  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 58 participants 59 participants 117 participants
72.6  (81.65) 76.8  (82.05) 74.7  (81.53)
Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 58 participants 58 participants 116 participants
9.6  (4.07) 9.6  (3.77) 9.6  (3.90)
[1]
Measure Description:

AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.

This data sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia).

[2]
Measure Analysis Population Description: Central reading was not available for one placebo patient.
Modified Craniocervical Dystonia Questionnaire (CDQ-24)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 58 participants 57 participants 115 participants
38.4  (20.41) 39.7  (18.17) 39.1  (19.26)
[1]
Measure Description: 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. Each of the 24 questions was rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 (no impairment) to 96 (severe impairment).
[2]
Measure Analysis Population Description: Baseline CDQ-24 was not completed by two placebo patients.
1.Primary Outcome
Title Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis
Hide Description

AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS 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, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.

A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point, treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. An unstructured covariance model was used.

Time Frame Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified ITT (mITT) Population was defined as all patients in the ITT Population who received study drug and had at least 1 centrally read post-baseline assessment of the AIMS from at least 1 scheduled post-baseline time point. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description:

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Number of Participants Analyzed 52 51
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.0  (0.45) -1.6  (0.46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SD-809, Placebo
Comments The linear mixed model for repeated measurements (MMRM) included fixed effects for treatment, each scheduled time point (5 levels: weeks 2, 4, 6, 9, and 12), the treatment-by-time point interaction, and the DRA status. Baseline AIMS score was a covariate. The unstructured covariance model was used, and the primary analysis compared the SD-809 and placebo groups at week 12. This was based on the F-test using the Satterhwaite method to compute the denominator degrees of freedom.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0188
Comments 5% level of significance (2-sided)
Method unstructured covariance
Comments [Not Specified]
Method of Estimation Estimation Parameter LSM difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-2.6 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.60
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)
Hide Description 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.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
modified intent to treat population
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description:

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Number of Participants Analyzed 56 57
Measure Type: Number
Unit of Measure: percentage of participants
48.2 40.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SD-809, Placebo
Comments The secondary efficacy endpoints were analyzed using a hierarchical testing procedure. If the primary analysis was statistically significant (p<0.05), then the first key secondary endpoint was to be analyzed. If the first key secondary endpoint was statistically significant, then the second key secondary endpoint was to be similarly analyzed. For any analysis that was not statistically significant, all subsequent analyses of key secondary endpoints were exploratory rather than confirmatory.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4001
Comments 5% level of significance (2-sided)
Method Pearson's chi-square test
Comments [Not Specified]
Method of Estimation Estimation Parameter Differences in %
Estimated Value 7.9
Confidence Interval (2-Sided) 95%
-10.2 to 25.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)
Hide Description 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.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
modified intent to treat population
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description:

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Number of Participants Analyzed 56 57
Measure Type: Number
Unit of Measure: percentage of participants
42.9 29.8
4.Secondary Outcome
Title Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24)
Hide Description 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 CDQ-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 (no impairment) to 96 (severe impairment). Negative change from baseline scores indicate improvement.
Time Frame Day 0 (Baseline), Week 12 with last observation carried forward
Hide Outcome Measure Data
Hide Analysis Population Description
modified intent to treat population
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description:

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Number of Participants Analyzed 56 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-11.1  (2.14) -8.3  (2.31)
5.Secondary Outcome
Title Participants With Adverse Events for the Overall Treatment Period
Hide Description 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.
Time Frame Day 1 to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description:

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Number of Participants Analyzed 58 59
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Treatment Period: any AE
41
  70.7%
36
  61.0%
Overall Treatment Period: SAE
3
   5.2%
5
   8.5%
Overall Treatment Period: Severe AE
3
   5.2%
3
   5.1%
Overall Treatment Period: treatment-related AE
28
  48.3%
21
  35.6%
Overall Treatment Period: Deaths
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis
Hide Description

AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS 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, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative percent change from baseline score indicates improvement.

The MMRM model includes fixed effects for treatment, time point (weeks 2, 4, 6, 9, 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. Patient is a random effect.

Time Frame Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
modified intent to treat population. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description:

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Number of Participants Analyzed 52 51
Least Squares Mean (Standard Error)
Unit of Measure: percentage change
-26.7  (6.06) -15.5  (6.26)
7.Secondary Outcome
Title Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12
Hide Description

Response level represents the % improvement in AIMS from baseline. AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS 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, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia).

Patients with a missing AIMS score were considered to be AIMS nonresponders.

Time Frame Day 0 (Baseline), Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
modified intent to treat population.
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description:

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Number of Participants Analyzed 56 57
Measure Type: Number
Unit of Measure: percentage of participants
>=10% 69.6 42.1
>=20% 50.0 29.8
>=30% 46.4 24.6
>=40% 32.1 22.8
>=50% 23.2 17.5
>=60% 19.6 8.8
>=70% 10.7 1.8
>=80% 8.9 1.8
>=90% 3.6 1.8
8.Secondary Outcome
Title Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis
Hide Description

This outcome is similar to the primary outcome except that AIMS was read locally.

AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. This outcome reports the local reading of AIMS data.

This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.

A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point (weeks 2, 4, 6, 9, and 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate.

Time Frame Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
modified intent to treat analysis. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description:

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Number of Participants Analyzed 52 51
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.9  (0.64) -3.7  (0.65)
Time Frame Day 1 to Week 12
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SD-809 Placebo
Hide Arm/Group Description

Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.

Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.

Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
All-Cause Mortality
SD-809 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/58 (0.00%)      0/59 (0.00%)    
Hide Serious Adverse Events
SD-809 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/58 (5.17%)      5/59 (8.47%)    
Infections and infestations     
Pneumonia  1  1/58 (1.72%)  1 1/59 (1.69%)  1
Abscess jaw  1  0/58 (0.00%)  0 1/59 (1.69%)  1
Injury, poisoning and procedural complications     
Overdose  1  0/58 (0.00%)  0 1/59 (1.69%)  1
Jaw fracture  1  0/58 (0.00%)  0 1/59 (1.69%)  1
Psychiatric disorders     
Schizophrenia  1  1/58 (1.72%)  1 0/59 (0.00%)  0
Mania  1  1/58 (1.72%)  1 0/59 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Laryngeal hypertrophy  1  0/58 (0.00%)  0 1/59 (1.69%)  1
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SD-809 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/58 (41.38%)      26/59 (44.07%)    
Gastrointestinal disorders     
Dry mouth  1  2/58 (3.45%)  2 6/59 (10.17%)  6
Diarrhoea  1  3/58 (5.17%)  3 3/59 (5.08%)  4
Vomiting  1  1/58 (1.72%)  1 3/59 (5.08%)  3
General disorders     
Fatigue  1  4/58 (6.90%)  4 5/59 (8.47%)  6
Infections and infestations     
Upper respiratory tract infection  1  2/58 (3.45%)  3 3/59 (5.08%)  3
Nervous system disorders     
Somnolence  1  8/58 (13.79%)  8 6/59 (10.17%)  8
Headache  1  3/58 (5.17%)  3 6/59 (10.17%)  6
Dizziness  1  2/58 (3.45%)  2 3/59 (5.08%)  3
Akathisia  1  3/58 (5.17%)  3 0/59 (0.00%)  0
Psychiatric disorders     
Anxiety  1  2/58 (3.45%)  2 4/59 (6.78%)  4
Insomnia  1  4/58 (6.90%)  4 1/59 (1.69%)  1
Skin and subcutaneous tissue disorders     
Rash  1  1/58 (1.72%)  1 3/59 (5.08%)  3
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc
Phone: 215-591-3000
EMail: ustevatrials@tevapharm.com
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Auspex Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02195700    
Other Study ID Numbers: SD-809-C-18
First Submitted: July 18, 2014
First Posted: July 21, 2014
Results First Submitted: January 3, 2018
Results First Posted: March 20, 2018
Last Update Posted: April 17, 2018