Addressing Involuntary Movements in Tardive Dyskinesia

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.

Time frame: Day 0 (Baseline), Weeks 2, 4, 8 and 12

Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. For this outcome, participants with baseline readings and during-study readings through Week 12 are included.

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.

Time frame: Day 0 (Baseline), Week 12

Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. One SD-809 12 mg/day participant was missing a baseline mCDQ-24.

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.

Time frame: Day 0 (Baseline), Week 12

Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment.

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

Population: The Safety Population was a subset of randomized participants and included all patients who were administered study drug (N=293).

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.

Time frame: Day 0 (Baseline), Week 12

Population: mITT population of participants. Participants with missing Week 12 data were considered non-responders.

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.

Time frame: Week 12

Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment.

The 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.

Time frame: Week 12

Population: mITT population

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.

Time frame: Day 0 (Baseline), Weeks 2, 4, 8 and 12

Population: The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. For this outcome, participants with baseline readings and during-study readings through Week 12 are included.