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NCT02291861: AIM-TD

Addressing Involuntary Movements in Tardive Dyskinesia

Completed Phase 3 Results posted Last updated 9 November 2021
What this trial tests

Phase 3 trial testing SD-809 in Tardive Dyskinesia in 298 participants. Completed in 19 August 2016.

Timeline
31 October 2014
Primary endpoint
19 August 2016
19 August 2016

Quick facts

Lead sponsorAuspex Pharmaceuticals, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment298
Start date31 October 2014
Primary completion19 August 2016
Estimated completion19 August 2016
Sites106 locations across Slovakia, Germany, Poland, Hungary, United States, Czechia

Drugs / interventions tested

Conditions studied

Sponsor

Auspex Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 18 to 80, any sex, with Tardive Dyskinesia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM) Primary · Day 0 (Baseline), Weeks 2, 4, 8 and 12

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 sc

GroupValue95% CI
Placebo-1.4± 0.41
SD-809 12 mg/Day-2.1± 0.42
SD-809 24 mg/Day-3.2± 0.45
SD-809 36 mg/Day-3.3± 0.42
Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC) Secondary · Week 12

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

GroupValue95% CI
Placebo2616.3 – 38.4
SD-809 12 mg/Day2818.5 – 40.8
SD-809 24 mg/Day4935.6 – 62.5
SD-809 36 mg/Day4431.4 – 56.7
Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score From Baseline to Week 12 Secondary · Day 0 (Baseline), Week 12

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 c

GroupValue95% CI
Placebo-7.1± 2.06
SD-809 12 mg/Day-5.8± 2.03
SD-809 24 mg/Day-10.2± 2.21
SD-809 36 mg/Day-10.7± 2.04
Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC) Secondary · Week 12

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

GroupValue95% CI
Placebo3120.6 – 43.8
SD-809 12 mg/Day2314.4 – 35.4
SD-809 24 mg/Day4531.9 – 58.7
SD-809 36 mg/Day4028.1 – 53.2
Percentage of Participants Who Had a 50% or Greater Reduction in Total Motor Abnormal Involuntary Movement Scale (AIMS) From Baseline to Week 12 Secondary · Day 0 (Baseline), Week 12

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 thr

GroupValue95% CI
Placebo126.0 – 22.9
SD-809 12 mg/Day136.9 – 24.2
SD-809 24 mg/Day3522.9 – 48.7
SD-809 36 mg/Day3321.8 – 45.9
Percent Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model for Repeated Measures (MMRM) Secondary · Day 0 (Baseline), Weeks 2, 4, 8 and 12

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 negati

GroupValue95% CI
Placebo-11.6± 4.32
SD-809 12 mg/Day-20.0± 4.34
SD-809 24 mg/Day-31.9± 4.73
SD-809 36 mg/Day-33.1± 4.38
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 Secondary · Day 0 (Baseline), Week 12

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 chang

10% Improvement
GroupValue95% CI
Placebo5037.5 – 62.5
SD-809 12 mg/Day6249.0 – 72.9
SD-809 24 mg/Day6753.4 – 78.8
SD-809 36 mg/Day7157.9 – 81.2
20% Improvement
GroupValue95% CI
Placebo4028.1 – 52.5
SD-809 12 mg/Day4734.6 – 59.1
SD-809 24 mg/Day5945.2 – 71.8
SD-809 36 mg/Day6046.8 – 71.9
30% Improvement
GroupValue95% CI
Placebo3120.6 – 43.8
SD-809 12 mg/Day3221.3 – 44.2
SD-809 24 mg/Day4935.6 – 62.5
SD-809 36 mg/Day4936.4 – 61.9
40% Improvement
GroupValue95% CI
Placebo168.4 – 26.9
SD-809 12 mg/Day2314.4 – 35.4
SD-809 24 mg/Day4531.9 – 58.7
SD-809 36 mg/Day4028.1 – 53.2
50% Improvement
GroupValue95% CI
Placebo126.0 – 22.9
SD-809 12 mg/Day136.9 – 24.2
SD-809 24 mg/Day3522.9 – 48.7
SD-809 36 mg/Day3321.8 – 45.9
60% Improvement
GroupValue95% CI
Placebo51.8 – 14.1
SD-809 12 mg/Day72.6 – 15.9
SD-809 24 mg/Day2011.5 – 33.6
SD-809 36 mg/Day1810.2 – 30.3
70% Improvement
GroupValue95% CI
Placebo20.0 – 9.2
SD-809 12 mg/Day30.4 – 11.5
SD-809 24 mg/Day124.6 – 24.8
SD-809 36 mg/Day167.8 – 28.8
80% Improvement
GroupValue95% CI
Placebo20.0 – 9.2
SD-809 12 mg/Day20.0 – 8.9
SD-809 24 mg/Day20.1 – 10.9
SD-809 36 mg/Day135.3 – 24.5
Participants With Adverse Events During the Overall Treatment Period Secondary · Day 1 to Week 12

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

Overall Treatment Period: any AE
GroupValue95% CI
Placebo34
SD-809 12 mg/Day36
SD-809 24 mg/Day32
SD-809 36 mg/Day38
Overall Treatment Period: SAE
GroupValue95% CI
Placebo4
SD-809 12 mg/Day2
SD-809 24 mg/Day6
SD-809 36 mg/Day4
Overall Treatment Period: Severe AE
GroupValue95% CI
Placebo2
SD-809 12 mg/Day2
SD-809 24 mg/Day4
SD-809 36 mg/Day1
Overall Treatment Period: treatment-related AE
GroupValue95% CI
Placebo19
SD-809 12 mg/Day13
SD-809 24 mg/Day11
SD-809 36 mg/Day18
Dose reduction because of AE
GroupValue95% CI
Placebo0
SD-809 12 mg/Day0
SD-809 24 mg/Day1
SD-809 36 mg/Day3
Dose suspension because of AE
GroupValue95% CI
Placebo2
SD-809 12 mg/Day3
SD-809 24 mg/Day1
SD-809 36 mg/Day1
Withdrawn from study because of AE
GroupValue95% CI
Placebo2
SD-809 12 mg/Day4
SD-809 24 mg/Day2
SD-809 36 mg/Day3

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 to Week 12. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 4/72 (6%)
Deaths: 0/72
SD-809 12 mg/Day
Serious: 2/74 (3%)
Deaths: 0/74
SD-809 24 mg/Day
Serious: 6/73 (8%)
Deaths: 1/73
SD-809 36 mg/Day
Serious: 4/74 (5%)
Deaths: 1/74

Serious adverse events (17 terms)

ReactionSystemPlaceboSD-809 12 mg/DaySD-809 24 mg/DaySD-809 36 mg/Day
Cardio-respiratory arrestCardiac disorders
Abdominal painGastrointestinal disorders
Pancreatic massGastrointestinal disorders
Alcohol interactionGeneral disorders
Sudden cardiac deathGeneral disorders
AppendicitisInfections and infestations
CellulitisInfections and infestations
PneumoniaInfections and infestations
Face injuryInjury, poisoning and procedural complications
Head injuryInjury, poisoning and procedural complications
Skeletal injuryInjury, poisoning and procedural complications
Neuroendocrine carcinoma metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Psychomotor hyperactivityNervous system disorders
Bipolar disorderPsychiatric disorders
DepressionPsychiatric disorders
Psychotic disorderPsychiatric disorders
Suicidal ideationPsychiatric disorders
Other adverse events (4 terms — click to expand)

ReactionSystemPlaceboSD-809 12 mg/DaySD-809 24 mg/DaySD-809 36 mg/Day
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
HeadacheNervous system disorders
NasopharyngitisInfections and infestations

Most-reported serious reactions: Cardio-respiratory arrest, Abdominal pain, Pancreatic mass, Alcohol interaction, Sudden cardiac death, Appendicitis, Cellulitis, Pneumonia.

Data from ClinicalTrials.gov NCT02291861 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether fixed-doses of an investigational drug, SD-809 (deutetrabenazine), will reduce the severity of abnormal involuntary movements of tardive dyskinesia.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Deuterium in drug discovery: progress, opportunities and challenges.
    Di Martino RMC, Maxwell BD, Pirali T. · · 2023 · cited 228× · PMID 37277503 · DOI 10.1038/s41573-023-00703-8
  2. Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial.
    Anderson KE, Stamler D, Davis MD, Factor SA, et al · · 2017 · cited 127× · PMID 28668671 · DOI 10.1016/s2215-0366(17)30236-5
  3. Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials.
    Solmi M, Pigato G, Kane JM, Correll CU. · · 2018 · cited 59× · PMID 29795977 · DOI 10.2147/dddt.s133205
  4. Miscellaneous treatments for antipsychotic-induced tardive dyskinesia.
    Soares-Weiser K, Rathbone J, Ogawa Y, Shinohara K, et al · · 2018 · cited 13× · PMID 29552749 · DOI 10.1002/14651858.cd000208.pub2
  5. Clinical Utility of Deutetrabenazine as a Treatment Option for Chorea Associated with Huntington's Disease and Tardive Dyskinesia.
    Frank S, Alakkas A. · · 2023 · cited 5× · PMID 38074485 · DOI 10.2147/tcrm.s279332
  6. Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated with Huntington Disease.
    Frank S, Anderson KE, Fernandez HH, Hauser RA, et al · · 2024 · cited 3× · PMID 38557959 · DOI 10.1007/s40120-024-00600-1
  7. Meeting Abstracts - Academy of Managed Care Pharmacy Nexus 2018.
    · 2018 · cited 1× · PMID 30295118 · DOI 10.18553/jmcp.2018.24.10-a.s1
  8. Analysis of clinical trials on drugs targeting dopamine receptors: a scoping review.
    Rajan T, Seifert R. · · 2026 · PMID 41105250 · DOI 10.1007/s00210-025-04710-x

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Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing