Clinical Trial Results:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF SD-809 (DEUTETRABENAZINE) FOR THE TREATMENT OF MODERATE TO SEVERE TARDIVE DYSKINESIA
|
Summary
|
|
EudraCT number |
2014-001890-15 |
Trial protocol |
CZ PL SK |
Global end of trial date |
21 May 2015
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
18 Mar 2017
|
First version publication date |
18 Mar 2017
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
SD-809-C-18
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02195700 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Auspex Pharmaceuticals, Inc
|
||
Sponsor organisation address |
3333 N. Torrey Pines Court, Ste. 400, La Jolla, CA, United States, 92037
|
||
Public contact |
Director, Clinical Research, Teva Branded Pharmaceuticals Products, R&D, Inc, 1 215-591-3000, ustevatrials@tevapharm.com
|
||
Scientific contact |
Director, Clinical Research, Teva Branded Pharmaceuticals Products, R&D, Inc, 1 215-591-3000, ustevatrials@tevapharm.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
30 Aug 2016
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
21 May 2015
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
• To evaluate the efficacy of SD-809 to reduce the severity of abnormal involuntary movements of Tardive Dyskinesia
• To evaluate the safety and tolerability of titration and maintenance therapy with SD-809 in subjects with drug-induced Tardive Dyskinesia
|
||
Protection of trial subjects |
This study was conducted in full accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (eg, Code of Federal Regulations [CFR] Title 21, Parts 50, 54, 56, 312, and 314; EU Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of GCP in the conduct of clinical trials on medicinal products for human use).
Written and/or oral information about the study was provided to all patients in a language understandable by the patients. The information included an adequate explanation of the aims, methods, anticipated benefits, potential hazards, and insurance arrangements in force. Written informed consent was obtained from each patient before any study procedures or assessments were done. It was explained to the patients that they were free to refuse entry into the study and free to withdraw from the study at any time without prejudice to future treatment.
Each patient’s willingness to participate in the study was documented in writing in a consent form that was signed by the patient with the date of that signature indicated. Each investigator kept the original consent forms, and copies were given to the patients.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Jun 2014
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Slovakia: 4
|
||
Country: Number of subjects enrolled |
Poland: 12
|
||
Country: Number of subjects enrolled |
Czech Republic: 4
|
||
Country: Number of subjects enrolled |
United States: 97
|
||
Worldwide total number of subjects |
117
|
||
EEA total number of subjects |
20
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
101
|
||
From 65 to 84 years |
16
|
||
85 years and over |
0
|
||
|
||||||||||||||||||||||||||||||||||||||||
|
Recruitment
|
||||||||||||||||||||||||||||||||||||||||
Recruitment details |
- | |||||||||||||||||||||||||||||||||||||||
|
Pre-assignment
|
||||||||||||||||||||||||||||||||||||||||
Screening 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. | |||||||||||||||||||||||||||||||||||||||
|
Period 1
|
||||||||||||||||||||||||||||||||||||||||
Period 1 title |
Overall Trial (overall period)
|
|||||||||||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
This was a randomized, double blind, placebo controlled, parallel group study. Patients were randomly assigned to receive treatment with SD 809 or a matching placebo in a 1:1 ratio. Patients were randomly assigned to treatment through an Interactive Technology Response System (ITRS). Using this system ensured a balance across treatment groups; no effort was made to maintain a balance among treatment groups within a study center. No patient’s treatment assignment was unblinded during the study.
|
|||||||||||||||||||||||||||||||||||||||
|
Arms
|
||||||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||||||||
|
Arm title
|
SD-809 | |||||||||||||||||||||||||||||||||||||||
Arm 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). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
SD-809
|
|||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||
Other name |
deutetrabenazine
|
|||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
A tablet formulation of SD 809 was administered with food twice daily, approximately 10 hours apart during the day.
Starting dose level was 6 mg BID and adjusted over the 6-week titration period. Weekly dose adjustments for insufficient dyskinesia control were limited to increments of 6 mg per day and all dose levels were administered in 2 divided doses. The maximum total daily dose of SD 809 was 48 mg per day, unless the patient was receiving a strong CYP2D6 inhibitor, in which case the maximum total daily dose was 36 mg. Once adequate control of dyskinesia was achieved, the dose of study drug was not to be increased further. The optimal dose was continued for an additional 6 weeks of maintenance therapy.
|
|||||||||||||||||||||||||||||||||||||||
|
Arm title
|
Placebo | |||||||||||||||||||||||||||||||||||||||
Arm description |
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). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Placebo-treated patients received tablets identical in appearance to the SD-809 tablets which were administered with food twice daily, approximately 10 hours apart during the day.
Doses were adjusted over the 6-week titration period. Once adequate control of dyskinesia was achieved, the dose of study drug was not to be increased further. The optimal dose was continued for an additional 6 weeks of maintenance therapy.
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SD-809
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting 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). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
SD-809
|
||
Reporting 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). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
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). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment. | ||
Subject analysis set title |
SD-809 mITT
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set 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.
The modified intention-to-treat (mITT) population was defined as all randomized patients who received study drug and had at least 1 centrally read postbaseline assessment of the AIMS from at least 1 scheduled postbaseline time point.
|
||
Subject analysis set title |
Placebo mITT
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period.
The modified intention-to-treat (mITT) population was defined as all randomized patients who received study drug and had at least 1 centrally read postbaseline assessment of the AIMS from at least 1 scheduled postbaseline time point.
|
||
|
|||||||||||||
End point title |
Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score from Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis | ||||||||||||
End point description |
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. 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.
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.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Change in AIMS to Week 12 | ||||||||||||
Statistical analysis description |
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.
|
||||||||||||
Comparison groups |
SD-809 mITT v Placebo mITT
|
||||||||||||
Number of subjects included in analysis |
103
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0188 [1] | ||||||||||||
Method |
unstructured covariance | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.6 | ||||||||||||
upper limit |
-0.2 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.6
|
||||||||||||
| Notes [1] - 5% level of significance (2-sided) |
|||||||||||||
|
|||||||||||||
End point title |
Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC) | ||||||||||||
End point 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Trt Success at Week 12 | ||||||||||||
Statistical analysis description |
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.
|
||||||||||||
Comparison groups |
SD-809 mITT v Placebo mITT
|
||||||||||||
Number of subjects included in analysis |
113
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.4001 [2] | ||||||||||||
Method |
Pearson's chi-square test | ||||||||||||
Parameter type |
Differences in % | ||||||||||||
Point estimate |
7.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-10.2 | ||||||||||||
upper limit |
25.2 | ||||||||||||
| Notes [2] - 5% level of significance (2-sided) |
|||||||||||||
|
|||||||||||||
End point title |
Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC) | ||||||||||||
End point 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change from Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24) | ||||||||||||
End point 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 – 96. Negative change from baseline scores indicate improvement.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 0 (Baseline), Week 12 with last observation carried forward
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
End point title |
Participants with Adverse Events for the Overall Treatment Period | ||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Day 1 to Week 12
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [3] - Safety population [4] - Safety population |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Day 1 to Week 12
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SD-809
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting 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). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
20 May 2014 |
• Addition of video recording of AIMS assessment at week 2
• Addition of CGIC at week 2
• CDQ-24 endpoint reclassified as an additional secondary endpoint
• Addition of sensitivity analyses
• Addition of procedures for handling missing data
|
||
08 Jul 2014 |
• Title amended to provide a better description of the study
• Expansion of the role of the independent monitoring committee to include monitoring of all data, including safety data
• Modified excluded medications to better reflect medications likely to have significant interactions with SD-809 and/or directly oppose the effects of SD 809 based on known mechanism of action
• Added additional guidance on specific excluded anticholinergics and stimulants
• Removed exclusion of patients who previously did not respond to tetrabenazine or who discontinued tetrabenazine due to an AE that was considered related to tetrabenazine and was either moderate/severe in severity, or met criteria for an SAE
• Added exclusion for participation in any previous study of SD 809 in which patients received SD-809
• Revised time frame for prior suicidality from 5 years to 6 months
• Brief physical examination moved from screening visit to baseline visit
• Specified that UPDRS III (motor), BARS, and ESS were to be performed at the investigator’s discretion at unscheduled visits
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
