Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44043   clinical trials with a EudraCT protocol, of which   7319   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia

    Summary
    EudraCT number
    		 2014-003135-19
    Trial protocol
    		 SK   PL   CZ   HU   DE  
    Global end of trial date
    19 Aug 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Jul 2018
    First version publication date
    19 Jul 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SD-809-C-23
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02291861
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Auspex Pharmaceuticals, Inc.
    Sponsor organisation address
    3333 N. Torrey Pines Court, Suite 400, La Jolla, California, United States, 92037
    Public contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, 001 2155913000, info.era-clinical@teva.de
    Scientific contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, 001 2155913000, info.era-clinical@teva.de
    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
    20 Dec 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Aug 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objectives of this study were: - To evaluate the efficacy of fixed doses of SD-809 to reduce the severity of abnormal involuntary movements of TD - To evaluate the safety and tolerability of fixed doses of SD-809 in patients with TD
    Protection of trial subjects
    This study was conducted in full accordance with the International Council on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (eg, Code of Federal Regulations 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). Each investigator was responsible for performing the study in accordance with the protocol, ICH guidelines, and GCP, and for collecting, recording, and reporting the data accurately and properly. 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
    29 Oct 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
    Czech Republic: 24
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Hungary: 17
    Country: Number of subjects enrolled
    Poland: 84
    Country: Number of subjects enrolled
    Slovakia: 8
    Country: Number of subjects enrolled
    United States: 161
    Worldwide total number of subjects
    298
    EEA total number of subjects
    137
    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)
    226
    From 65 to 84 years
    72
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 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.

    Pre-assignment
    Screening details
    		 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.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    During the treatment period the sponsor, patients, as well as the investigators and their site personnel were blinded to treatment assignment. Active and placebo study drug were identical in appearance and packaged in study drug kits according to the randomization code

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Placebo tablets taken twice daily for 12 weeks.
    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 tablets taken twice daily for 12 weeks. Tablets were swallowed whole with water and taken with food.

    Arm title
    		 SD-809 12 mg/day
    Arm description
    		 SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SD-809
    Investigational medicinal product code
    Other name
    deutetrabenzine, Austedo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    SD-809 tablets dose titrated for 4 weeks until target randomized dose is reached. The dose is maintained for an additional 8 weeks. Tablets were swallowed whole with water and taken with food.

    Arm title
    		 SD-809 24 mg/day
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SD-809
    Investigational medicinal product code
    Other name
    deutetrabenzine, Austedo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    SD-809 tablets dose titrated for 4 weeks until target randomized dose is reached. The dose is maintained for an additional 8 weeks. Tablets were swallowed whole with water and taken with food.

    Arm title
    		 SD-809 36 mg/day
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SD-809
    Investigational medicinal product code
    Other name
    deutetrabenzine, Austedo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    SD-809 tablets dose titrated for 4 weeks until target randomized dose is reached. The dose is maintained for an additional 8 weeks. Tablets were swallowed whole with water and taken with food.

    Number of subjects in period 1
    		Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Started
    74
    75
    74
    75
    Safety population
    72
    74
    73
    74
    Completed
    67
    67
    65
    65
    Not completed
    7
    8
    9
    10
         Adverse event, serious fatal
    -
    -
    1
    1
         Consent withdrawn by subject
    1
    2
    1
    4
         Adverse event, non-fatal
    2
    4
    1
    2
         Not specified
    -
    -
    -
    1
         Lost to follow-up
    2
    1
    4
    -
         Protocol deviation
    1
    -
    -
    1
         Noncompliance
    1
    1
    2
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo tablets taken twice daily for 12 weeks.

    Reporting group title
    SD-809 12 mg/day
    Reporting group description
    		 SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.

    Reporting group title
    SD-809 24 mg/day
    Reporting group description
    		 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.

    Reporting group title
    SD-809 36 mg/day
    Reporting group description
    		 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.

    Reporting group values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day Total
    Number of subjects
    		 74 75 74 75 298
    Age categorical
    Units: Subjects
        < 21 years
    		 0 0 0 0 0
        21 - 81 years
    		 74 75 74 75 298
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 54.6 ± 11.92 57.0 ± 9.89 55.5 ± 11.29 58.2 ± 11.48 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 37 42 42 42 163
        Male
    		 37 33 32 33 135
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 1 1 0 2 4
        Asian
    		 0 0 0 0 0
        Black or African American
    		 14 16 20 10 60
        Native Hawaiian or Pacific Islander
    		 0 0 0 0 0
        White
    		 59 58 54 61 232
        Other
    		 0 0 0 2 2
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or latino
    		 7 6 3 8 24
        Not hispanic or latino
    		 66 65 70 65 266
        Not reported
    		 0 3 1 1 5
        Unknown
    		 1 1 0 1 3
    Education Level
    Units: Subjects
        <= 12 years
    		 41 45 44 40 170
        > 12 years
    		 33 30 30 35 128
    Use of a Dopamine Receptor Antagonist
    The randomization was stratified by baseline use of DRA (currently taking versus not currently taking a DRA).
    Units: Subjects
        Yes - Use of DRA
    		 58 57 58 54 227
        No Use of DRA
    		 16 18 16 21 71
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 82.5 ± 18.52 80.9 ± 20.87 86.8 ± 18.66 78.5 ± 17.45 -
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 168.5 ± 9.18 168.0 ± 10.93 168.5 ± 9.43 167.7 ± 10.52 -
    Body Mass Index
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 29.04 ± 6.158 28.63 ± 6.791 30.71 ± 6.992 27.97 ± 6.138 -
    Time Since Tardive Dyskinesia (TD) Diagnosis
    Units: years
        arithmetic mean (standard deviation)
    		 5.98 ± 5.291 5.49 ± 5.389 4.93 ± 6.012 6.23 ± 6.059 -
    Total Motor Abnormal Involuntary Movement Scale (AIMS) Score
    The 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. Total Motor assessment 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.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 8.6 ± 3.24 8.5 ± 3.18 7.6 ± 3.50 8.6 ± 3.82 -
    Modified Craniocervical Dystonia Questionnaire (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. 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 – 96.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 40.9 ± 19.90 36.8 ± 20.36 34.4 ± 19.45 34.8 ± 18.23 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo tablets taken twice daily for 12 weeks.

    Reporting group title
    SD-809 12 mg/day
    Reporting group description
    		 SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.

    Reporting group title
    SD-809 24 mg/day
    Reporting group description
    		 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.

    Reporting group title
    SD-809 36 mg/day
    Reporting group description
    		 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.

    Primary: Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score from Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM)

    		 Close Top of page
    End point title
    		 Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score from Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM)
    End point description
    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.
    End point type
    Primary
    End point timeframe
    Day 0 (Baseline), Weeks 2, 4, 8 and 12
    End point values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Number of subjects analysed
    56 [1]
    53 [2]
    45 [3]
    52 [4]
    Units: units on a scale
        least squares mean (standard error)
    -1.4 ± 0.41
    -2.1 ± 0.42
    -3.2 ± 0.45
    -3.3 ± 0.42
    Notes
    [1] - mITT Population Participants with baseline and during-study readings through Week 12
    [2] - mITT Population Participants with baseline and during-study readings through Week 12
    [3] - mITT Population Participants with baseline and during-study readings through Week 12
    [4] - mITT Population Participants with baseline and during-study readings through Week 12
    Statistical analysis title
    		 Placebo, SD-809 36 mg/Day
    Statistical analysis description
    A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. The primary endpoint compared the change in total motor AIMS score from baseline to week 12 between the SD-809 36 mg/day group and the placebo group.
    Comparison groups
    Placebo v SD-809 36 mg/day
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [5]
    Method
    		 mixed model for repeated measures
    Parameter type
    		 LSM difference
    Point estimate
    -1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.09
         upper limit
    		 -0.79
    Notes
    [5] - 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.
    Statistical analysis title
    		 Placebo, SD-809 24 mg/Day
    Statistical analysis description
    A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the change in total motor AIMS score from baseline to week 12 between the SD-809 24 mg/day group and the placebo group, and is the third analysis in the fixed-sequence.
    Comparison groups
    Placebo v SD-809 24 mg/day
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003 [6]
    Method
    		 mixed model for repeated measures
    Parameter type
    		 LSM difference
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 -0.63
    Notes
    [6] - 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.
    Statistical analysis title
    		 Placebo, SD-809 12 mg/Day
    Statistical analysis description
    A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the change in total motor AIMS score from baseline to week 12 between the SD-809 12 mg/day group and the placebo group, and is the fifth analysis in the fixed-sequence.
    Comparison groups
    Placebo v SD-809 12 mg/day
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.217 [7]
    Method
    		 mixed model for repeated measures
    Parameter type
    		 LSM difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.84
         upper limit
    		 0.42
    Notes
    [7] - 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.

    Secondary: Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)

    		 Close Top of page
    End point title
    		 Percentage of Patients Considered 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. The success 95% confidence interval (CI) was calculated with the Wilson (score) confidence limits.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Number of subjects analysed
    58 [8]
    60 [9]
    49 [10]
    55 [11]
    Units: percentage of participants
        number (confidence interval 95%)
    26 (16.3 to 38.4)
    28 (18.5 to 40.8)
    49 (35.6 to 62.5)
    44 (31.4 to 56.7)
    Notes
    [8] - mITT population
    [9] - mITT population
    [10] - mITT population
    [11] - mITT population
    Statistical analysis title
    		 Placebo, SD-809 36 mg/Day
    Statistical analysis description
    A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the percentage of patients considered a treatment success at week 12 between the SD-809 36 mg/day group and the placebo group, and is the second analysis in the fixed-sequence.
    Comparison groups
    Placebo v SD-809 36 mg/day
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.059 [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 4.645
    Notes
    [12] - The statistical test was a Cochran-Mantel-Haenszel (CMH) test stratified by baseline use of dopamine receptor antagonist (DRAs).
    Statistical analysis title
    		 Placebo, SD-809 24 mg/Day
    Statistical analysis description
    A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the percentage of patients considered a treatment success at week 12 between the SD-809 24 mg/day group and the placebo group, and is the fourth analysis in the fixed-sequence.
    Comparison groups
    Placebo v SD-809 24 mg/day
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.014 [13]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.211
         upper limit
    		 6.052
    Notes
    [13] - The statistical test was a CMH test stratified by baseline use of DRAs.
    Statistical analysis title
    		 Placebo, SD-809 12 mg/Day
    Statistical analysis description
    A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the percentage of patients considered a treatment success at week 12 between the SD-809 12 mg/day group and the placebo group, and is the sixth (last) analysis in the fixed-sequence.
    Comparison groups
    Placebo v SD-809 12 mg/day
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.734 [14]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.509
         upper limit
    		 2.61
    Notes
    [14] - The statistical test was a CMH test stratified by baseline use of DRAs.

    Secondary: Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score from Baseline to Week 12

    		 Close Top of page
    End point title
    		 Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score from Baseline to Week 12
    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 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.
    End point type
    Secondary
    End point timeframe
    Day 0 (Baseline), Week 12
    End point values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Number of subjects analysed
    58 [15]
    59 [16]
    49 [17]
    55 [18]
    Units: units on a scale
        least squares mean (standard error)
    -7.1 ± 2.06
    -5.8 ± 2.03
    -10.2 ± 2.21
    -10.7 ± 2.04
    Notes
    [15] - mITT Population
    [16] - mITT Population One participant was missing a baseline mCDQ-24.
    [17] - mITT Population
    [18] - mITT Population
    Statistical analysis title
    		 Placebo, SD-809 36 mg/Day
    Comparison groups
    Placebo v SD-809 36 mg/day
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.207 [19]
    Method
    		 ANCOVA
    Parameter type
    		 LSM difference
    Point estimate
    -3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.18
         upper limit
    		 2
    Notes
    [19] - 5% level of significance (2-sided) ANCOVA with treatment group and baseline use of DRAs as fixed effects and the baseline value as a covariate.
    Statistical analysis title
    		 Placebo, SD-809 24 mg/Day
    Comparison groups
    Placebo v SD-809 24 mg/day
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.281 [20]
    Method
    		 ANCOVA
    Parameter type
    		 LSM difference
    Point estimate
    -3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.86
         upper limit
    		 2.59
    Notes
    [20] - 5% level of significance (2-sided) ANCOVA with treatment group and baseline use of DRAs as fixed effects and the baseline value as a covariate.
    Statistical analysis title
    		 Placebo, SD-809 12 mg/Day
    Comparison groups
    Placebo v SD-809 12 mg/day
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.627 [21]
    Method
    		 ANCOVA
    Parameter type
    		 LSM difference
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.1
         upper limit
    		 6.79
    Notes
    [21] - 5% level of significance (2-sided) ANCOVA with treatment group and baseline use of DRAs as fixed effects and the baseline value as a covariate.

    Secondary: Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)

    		 Close Top of page
    End point title
    		 Percentage of Patients Considered 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. The success 95% CI was calculated with the Wilson (score) confidence limits.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Number of subjects analysed
    58 [22]
    60 [23]
    49 [24]
    55 [25]
    Units: percentage of participants
        number (confidence interval 95%)
    31 (20.6 to 43.8)
    23 (14.4 to 35.4)
    45 (31.9 to 58.7)
    40 (28.1 to 53.2)
    Notes
    [22] - mITT population
    [23] - mITT population
    [24] - mITT population
    [25] - mITT population
    Statistical analysis title
    		 Placebo, SD-809 36 mg/Day
    Comparison groups
    Placebo v SD-809 36 mg/day
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.296 [26]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.694
         upper limit
    		 3.285
    Notes
    [26] - 5% level of significance (2-sided) CMH test stratified by baseline use of DRAs.
    Statistical analysis title
    		 Placebo, SD-809 24 mg/Day
    Comparison groups
    Placebo v SD-809 24 mg/day
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.134 [27]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.826
         upper limit
    		 3.994
    Notes
    [27] - 5% level of significance (2-sided) CMH test stratified by baseline use of DRAs.
    Statistical analysis title
    		 Placebo, SD-809 12 mg/Day
    Comparison groups
    Placebo v SD-809 12 mg/day
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.372 [28]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.302
         upper limit
    		 1.563
    Notes
    [28] - 5% level of significance (2-sided) CMH test stratified by baseline use of DRAs.

    Secondary: Percentage of Participants Who Had a 50% or Greater Reduction in Total Motor Abnormal Involuntary Movement Scale (AIMS) From Baseline to Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Had a 50% or Greater Reduction in Total Motor Abnormal Involuntary Movement Scale (AIMS) From Baseline to Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Day 0 (Baseline), Week 12
    End point values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Number of subjects analysed
    58 [29]
    60 [30]
    49 [31]
    55 [32]
    Units: percentage of participants
        number (confidence interval 95%)
    12 (6.0 to 22.9)
    13 (6.9 to 24.2)
    35 (22.9 to 48.7)
    33 (21.8 to 45.9)
    Notes
    [29] - mITT population. Participants with missing Week 12 data were considered non-responders.
    [30] - mITT population. Participants with missing Week 12 data were considered non-responders.
    [31] - mITT population. Participants with missing Week 12 data were considered non-responders.
    [32] - mITT population. Participants with missing Week 12 data were considered non-responders.
    Statistical analysis title
    		 Placebo, SD-809 36 mg/Day
    Comparison groups
    Placebo v SD-809 36 mg/day
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007 [33]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.395
         upper limit
    		 10.359
    Notes
    [33] - 5% level of significance (2-sided) CMH test stratified by baseline use of DRAs.
    Statistical analysis title
    		 Placebo, SD-809 24 mg/Day
    Comparison groups
    Placebo v SD-809 24 mg/day
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005 [34]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.46
         upper limit
    		 10.716
    Notes
    [34] - 5% level of significance (2-sided) CMH test stratified by baseline use of DRAs.
    Statistical analysis title
    		 Placebo, SD-809 12 mg/Day
    Comparison groups
    Placebo v SD-809 12 mg/day
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.829 [35]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.383
         upper limit
    		 3.316
    Notes
    [35] - 5% level of significance (2-sided) CMH test stratified by baseline use of DRAs.

    Secondary: Percent Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score from Baseline to Week 12 Using a Mixed Model for Repeated Measures (MMRM)

    		 Close Top of page
    End point title
    		 Percent Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score from Baseline to Week 12 Using a Mixed Model for Repeated Measures (MMRM)
    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 (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.
    End point type
    Secondary
    End point timeframe
    Day 0 (Baseline), Weeks 2, 4, 8 and 12
    End point values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Number of subjects analysed
    56 [36]
    53 [37]
    45 [38]
    52 [39]
    Units: percentage of baseline
        least squares mean (standard error)
    -11.6 ± 4.32
    -20.0 ± 4.34
    -31.9 ± 4.73
    -33.1 ± 4.38
    Notes
    [36] - mITT population; participants with baseline and data through Week 12 are included.
    [37] - mITT population; participants with baseline and data through Week 12 are included.
    [38] - mITT population; participants with baseline and data through Week 12 are included.
    [39] - mITT population; participants with baseline and data through Week 12 are included.
    Statistical analysis title
    		 Placebo, SD-809 36 mg/Day
    Comparison groups
    Placebo v SD-809 36 mg/day
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [40]
    Method
    		 mixed model for repeated measures
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -21.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33.44
         upper limit
    		 -9.52
    Notes
    [40] - 5% level of significance (2-sided). 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.
    Statistical analysis title
    		 Placebo, SD-809 24 mg/Day
    Comparison groups
    Placebo v SD-809 24 mg/day
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [41]
    Method
    		 mixed model for repeated measures
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -20.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.57
         upper limit
    		 -7.92
    Notes
    [41] - 5% level of significance (2-sided). 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.
    Statistical analysis title
    		 Placebo, SD-809 12 mg/Day
    Comparison groups
    Placebo v SD-809 12 mg/day
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.16 [42]
    Method
    		 mixed model for repeated measures
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -8.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.15
         upper limit
    		 3.34
    Notes
    [42] - 5% level of significance (2-sided). 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.

    Secondary: 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

    		 Close Top of page
    End point title
    		 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
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Day 0 (Baseline), Week 12
    End point values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Number of subjects analysed
    58 [43]
    60 [44]
    49 [45]
    55 [46]
    Units: percentage of participants
    number (confidence interval 95%)
        10% Improvement|
    50 (37.5 to 62.5)
    62 (49.0 to 72.9)
    67 (53.4 to 78.8)
    71 (57.9 to 81.2)
        20% Improvement|
    40 (28.1 to 52.5)
    47 (34.6 to 59.1)
    59 (45.2 to 71.8)
    60 (46.8 to 71.9)
        30% Improvement|
    31 (20.6 to 43.8)
    32 (21.3 to 44.2)
    49 (35.6 to 62.5)
    49 (36.4 to 61.9)
        40% Improvement|
    16 (8.4 to 26.9)
    23 (14.4 to 35.4)
    45 (31.9 to 58.7)
    40 (28.1 to 53.2)
        50% Improvement|
    12 (6.0 to 22.9)
    13 (6.9 to 24.2)
    35 (22.9 to 48.7)
    33 (21.8 to 45.9)
        60% Improvement|
    5 (1.8 to 14.1)
    7 (2.6 to 15.9)
    20 (11.5 to 33.6)
    18 (10.2 to 30.3)
        70% Improvement|
    2 (0.0 to 9.2)
    3 (0.4 to 11.5)
    12 (4.6 to 24.8)
    16 (7.8 to 28.8)
        80% Improvement|
    2 (0.0 to 9.2)
    2 (0.0 to 8.9)
    2 (0.1 to 10.9)
    13 (5.3 to 24.5)
        90% Improvement|
    2 (0.0 to 9.2)
    0 (0.0 to 6.0)
    0 (0.0 to 7.3)
    5 (1.1 to 15.1)
    Notes
    [43] - mITT population
    [44] - mITT population
    [45] - mITT population
    [46] - mITT population
    No statistical analyses for this end point

    Secondary: Participants with Adverse Events During the Overall Treatment Period

    		 Close Top of page
    End point title
    		 Participants with Adverse Events During 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
    End point values
    		 Placebo SD-809 12 mg/day SD-809 24 mg/day SD-809 36 mg/day
    Number of subjects analysed
    72 [47]
    74 [48]
    73 [49]
    74 [50]
    Units: participants
        Overall Treatment Period: any AE|
    34
    36
    32
    38
        Overall Treatment Period: SAE|
    4
    2
    6
    4
        Overall Treatment Period: Severe AE|
    2
    2
    4
    1
        Overall Treatment Period: treatment-related AE|
    19
    13
    11
    18
        Dose reduction because of AE|
    0
    0
    1
    3
        Dose suspension because of AE|
    2
    3
    1
    1
        Withdrawn from study because of AE|
    2
    4
    2
    3
    Notes
    [47] - Safety population
    [48] - Safety population
    [49] - Safety population
    [50] - Safety population
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    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 12 mg/day
    Reporting group description
    		 SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo tablets taken twice daily for 12 weeks.

    Reporting group title
    SD-809 24 mg/day
    Reporting group description
    		 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.

    Reporting group title
    SD-809 36 mg/day
    Reporting group description
    		 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.

    Serious adverse events
    		 SD-809 12 mg/day Placebo SD-809 24 mg/day SD-809 36 mg/day
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 74 (2.70%)
    4 / 72 (5.56%)
    6 / 73 (8.22%)
    4 / 74 (5.41%)
         number of deaths (all causes)
    0
    0
    1
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neuroendocrine carcinoma metastatic
         subjects affected / exposed
    0 / 74 (0.00%)
    1 / 72 (1.39%)
    0 / 73 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Face injury
         subjects affected / exposed
    1 / 74 (1.35%)
    0 / 72 (0.00%)
    0 / 73 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 74 (0.00%)
    1 / 72 (1.39%)
    0 / 73 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skeletal injury
         subjects affected / exposed
    1 / 74 (1.35%)
    0 / 72 (0.00%)
    0 / 73 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    0 / 73 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Nervous system disorders
    Psychomotor hyperactivity
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    0 / 73 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Alcohol interaction
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    0 / 73 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    1 / 73 (1.37%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 74 (0.00%)
    1 / 72 (1.39%)
    0 / 73 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic mass
         subjects affected / exposed
    0 / 74 (0.00%)
    1 / 72 (1.39%)
    0 / 73 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Bipolar disorder
         subjects affected / exposed
    0 / 74 (0.00%)
    1 / 72 (1.39%)
    0 / 73 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    1 / 73 (1.37%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 74 (1.35%)
    0 / 72 (0.00%)
    0 / 73 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    1 / 73 (1.37%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    1 / 73 (1.37%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    1 / 73 (1.37%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 74 (0.00%)
    0 / 72 (0.00%)
    1 / 73 (1.37%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 SD-809 12 mg/day Placebo SD-809 24 mg/day SD-809 36 mg/day
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 74 (12.16%)
    14 / 72 (19.44%)
    9 / 73 (12.33%)
    10 / 74 (13.51%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 74 (6.76%)
    4 / 72 (5.56%)
    2 / 73 (2.74%)
    5 / 74 (6.76%)
         occurrences all number
    7
    4
    3
    5
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 74 (1.35%)
    2 / 72 (2.78%)
    3 / 73 (4.11%)
    5 / 74 (6.76%)
         occurrences all number
    1
    2
    4
    6
    Nausea
         subjects affected / exposed
    1 / 74 (1.35%)
    7 / 72 (9.72%)
    1 / 73 (1.37%)
    1 / 74 (1.35%)
         occurrences all number
    1
    8
    1
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 74 (5.41%)
    1 / 72 (1.39%)
    3 / 73 (4.11%)
    2 / 74 (2.70%)
         occurrences all number
    4
    1
    3
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Aug 2014
    Amendment 1 (dated 28 August 2014) was issued before the enrollment period began; no patients were enrolled into the study while this amendment was in effect. - Removal of video recording of AIMS assessment at week 13 - Measurement of orthostatic BP and pulse to be performed after the patient was in the supine position for at least 5 minutes and the standing position for at least 3 minutes - Change of timing of blood sampling for pharmacokinetic assessments to include scheduled visits at weeks 8 and 12 only - Requirement of a 12-lead ECG for all patients, regardless of the use of drugs that prolong the QT interval, at weeks 2, 4, and 8 - Clarification that dose suspensions or decreases for patients who experienced an adverse event or clinically significant adverse event were to be made by the investigator - Removal of the interactive web response system as the mechanism for randomization, change of doses, and re-ordering of study drug - Addition of IRT for randomization and dose changes - Modified to allow study drug to only be dispensed at clinic visits (a 2-week supply at baseline and week 2, a 4-week supply at week 4 and week 8, and a new supply for dose reductions as needed at unscheduled visits) - Removal of a maximal dose of SD-809 of 36 mg/day (or matching placebo) for patients receiving strong CYP2D6 inhibitors
    15 Sep 2014
    Amendment 2 (dated 15 September 2014) also was issued before any patients were enrolled into the study; all patients enrolled while this amendment was in effect. - Removal of AIMS at week 13 - HADS and C-SSRS required at unscheduled visits - Addition of the following assessments at the investigator’s discretion at unscheduled visits, if required: AIMS, video recording of AIMS, CGIC, PGIC, MoCA, mCDQ-24, assessment of study drug accountability and compliance and collection of all study drug if a dose reduction is required (maintenance period only), and provide diary card and remind patients to complete their diary card and bring to their next clinic visit (if unscheduled visit is replacing the week 4 or week 8 visits) - Addition of the following laboratory tests at the investigator’s discretion at unscheduled visits, if required: UDS, pregnancy test (women of childbearing potential only), virology screen (HBsAg), and prothrombin time (with INR)
    29 Oct 2015
    Amendment 3 was approved on 29 October 2015; 102 patients enrolled into the study while this amendment was in effect. Changes to the protocol were considered to have no negative impact on the safety of patients already enrolled into the study at that time. - Increase in the number of study sites from approximately 60 to approximately 75 and the number of patients from approximately 200 to approximately 288 - Increase in the upper limit of age for inclusion in the study to 80 years of age - Clarification that patients with a positive UDS were not excluded if they had a valid corresponding prescription for a medical condition - Removal of blinded interim analysis of variability - Change from co-primary analyses to a single primary analysis using a 2-sided test at the alpha=0.05 level.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/28668671
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA