Reducing Involuntary Movements in Participants With Tardive Dyskinesia
- Registration Number
- NCT02198794
- Lead Sponsor
- Auspex Pharmaceuticals, Inc.
- Brief Summary
The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of SD-809 in reducing the severity of abnormal involuntary movements of moderate to severe tardive dyskinesia. The purpose of part B is to establish the durability of effect of SD-809 following 1-week period of randomized withdrawal (SD-809 and placebo), followed by 12 weeks of maintenance with SD-809.
- Detailed Description
Participants who complete study SD-809-C-18 (NCT02195700), SD-809-C-23 (NCT02291861), or any other SD-809 study will be enrolled in this study. This study include a screening period (Part A), a titration period (Part A), a long-term treatment period (Part A), a double-blind, randomized withdrawal period (Part B), treatment after completion of the randomized withdrawal period (Part B), and a post-treatment safety follow-up period (Part A and Part B). EU participants who complete Part B will be invited to participate in Part C.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 343
- History of using a dopamine receptor antagonist for at least 3 months
- Clinical diagnosis of tardive dyskinesia and has had symptoms for at least 3 months prior to screening
- Participant has successfully completed a controlled study of SD-809 for treatment of moderate to severe tardive dyskinesia
- Participants with underlying psychiatric diagnosis are stable and have no change in psychoactive medications
- Have a mental health provider and does not anticipate any changes to treatment regimen in the next 3 months
- History of being compliant with prescribed medications
- Able to swallow study drug whole
- Be in good general health and is expected to attend all study visits and complete study assessments
- Female participants must not be pregnant and agree to an acceptable method of contraception
- Currently receiving medication for the treatment of tardive dyskinesia
- Have a neurological condition other than tardive dyskinesia that may interfere with assessing the severity of dyskinesias
- Have a serious untreated or undertreated psychiatric illness
- Have recent history or presence of violent behavior
- Have unstable or serious medical illness
- Have evidence of hepatic impairment
- Have evidence of renal impairment
- Have known allergy to any component of SD-809 or tetrabenazine
- Has participated in an investigational drug or device trial (other than Study C-18, Study C-23, or any other eligible TEV-50717 parent study) and received study drug within 30 days
- Have acknowledged use of illicit drugs
- Have a history of alcohol or substance abuse in the previous 12 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: SD-809 SD-809 Participants will receive SD-809 orally twice daily (BID) starting at 12 mg/day, which will be titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who decline to participate in Part B, will continue at their stable dose of SD-809 BID up to Week 158. Part B: Placebo SD-809 Participants will receive placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter will receive SD-809 (stable dose) for 12 weeks. Part B: Placebo Placebo Participants will receive placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter will receive SD-809 (stable dose) for 12 weeks. Part B: SD-809 SD-809 Participants will receive SD-809 (stable dose) for 1 week in randomized withdrawal period and will continue to receive the same dose of SD-809 for an additional 12 weeks. Part C: SD-809 SD-809 EU participants who complete Part B and willing to continue in the study will continue treatment with SD-809 for 52 weeks at the dose administered during the 12-week open-label period of Part B.
- Primary Outcome Measures
Name Time Method Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) AEs were analyzed as one group combined for parts A and B per planned analysis. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=prevents normal daily activities. Drug-related TEAEs: TEAEs with possible, probable, or definite relationship to study drug. Serious AEs: death, a life-threatening AE, 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 participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A treatment-emergent AE was defined as an AE that began after the first administration of study medication or existing AEs that worsened after the first dose of study medication. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating Day 1 of Part B, Day 7 of Part B 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. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
- Secondary Outcome Measures
Name Time Method Part A: Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating Baseline, Week 145 The AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating Baseline, Week 158 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. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating Baseline, Week 145 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. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating Baseline, Week 158 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. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Percentage of Participants Who Had a 50% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating Baseline to Week 145 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. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Percentage of Participants Who Had a 70% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating Baseline to Week 145 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. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating Baseline, Week 145 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. Items 8 to 10 deal with global severity as judged by the examiner, and the participant's awareness of the movements and the distress associated with them. Item 8 (used as an overall severity index indicating severity of abnormal movements) was rated on a 5-point anchored scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 9 and 10 (provide additional information with regard to participant's incapacitation due to abnormal movements and participant's awareness of abnormal movements) were rated on a 5-point anchored scale ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Higher scores indicated more severe disease.
Part A: Percentage of Participants Who Were a Treatment Success, Based on the Clinical Global Impression of Change (CGIC) Baseline up to Week 145 A treatment success was defined as much or very much improved on the CGIC from baseline of this study. The CGIC is a single-item questionnaire that asks the investigator to assess a participant's TD symptoms at specific visits/weeks after initiating therapy. The CGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.
Part A: Percentage of Participants Who Were a Treatment Success, Based on the Patient Global Impression of Change (PGIC) Baseline up to Week 145 A treatment success was defined as much or very much improved on the PGIC from baseline of this study. The PGIC is single-item questionnaire that asks the participant to assess their TD symptoms at specific visits/weeks after initiating therapy. The PGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.
Part A: Change From Baseline in Modified CDQ-24 Score at Week 158 Baseline, Week 158 The CDQ-24 is a disease-specific quality of life questionnaire developed for use in participants 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 were 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 participants on a scale of 0 = never or no impairment to 4 = always or very severe impairment. Total score ranged from 0 - 96, with higher score indicative of severe impairment.
Trial Locations
- Locations (82)
Teva Investigational Site 144
🇺🇸Port Charlotte, Florida, United States
Teva Investigational Site 130
🇺🇸Oceanside, California, United States
Teva Investigational Site 145
🇺🇸Tuscaloosa, Alabama, United States
Teva Investigational Site 530
🇨🇿Prague 6, Czechia
Teva Investigational Site 108
🇺🇸Anaheim, California, United States
Teva Investigational Site 147
🇺🇸Los Angeles, California, United States
Teva Investigational Site 556
🇨🇿Hostivice, Czechia
Teva Investigational Site 522
🇵🇱Torun, Poland
Teva Investigational Site 516
🇵🇱Wroclaw, Poland
Teva Investigational Site 554
🇵🇱Bialystok, Poland
Teva Investigational Site 517
🇵🇱Choroszcz, Poland
Teva Investigational Site 550
🇵🇱Warszawa, Poland
Teva Investigational Site 162
🇺🇸Miami, Florida, United States
Teva Investigational Site 115
🇺🇸Salt Lake City, Utah, United States
Teva Investigational Site 141
🇺🇸Salt Lake City, Utah, United States
Teva Investigational Site 525
🇸🇰Hronovce, Slovakia
Teva Investigational Site 526
🇸🇰Roznava, Slovakia
Teva Investigational Site 529
🇸🇰Bratislava, Slovakia
Teva Investigational Site 107
🇺🇸Anaheim, California, United States
Teva Investigational Site 121
🇺🇸Los Angeles, California, United States
Teva Investigational Site 123
🇺🇸Glendale, California, United States
Teva Investigational Site 174
🇺🇸Norwalk, California, United States
Teva Investigational Site 102
🇺🇸Orange, California, United States
Teva Investigational Site 104
🇺🇸San Bernardino, California, United States
Teva Investigational Site 110
🇺🇸San Diego, California, United States
Teva Investigational Site 157
🇺🇸Boca Raton, Florida, United States
Teva Investigational Site 156
🇺🇸Washington, District of Columbia, United States
Teva Investigational Site 153
🇺🇸Miami, Florida, United States
Teva Investigational Site 150
🇺🇸Lake City, Florida, United States
Teva Investigational Site 154
🇺🇸Baltimore, Maryland, United States
Teva Investigational Site 118
🇺🇸Creve Coeur, Missouri, United States
Teva Investigational Site 101
🇺🇸Glen Burnie, Maryland, United States
Teva Investigational Site 161
🇺🇸Saint Louis, Missouri, United States
Teva Investigational Site 114
🇺🇸Garfield Heights, Ohio, United States
Teva Investigational Site 151
🇺🇸Fort Worth, Texas, United States
Teva Investigational Site 559
🇨🇿Havirov, Czechia
Teva Investigational Site 167
🇺🇸Richland, Washington, United States
Teva Investigational Site 535
🇨🇿Litomerice, Czechia
Teva Investigational Site 533
🇨🇿Prague 10, Czechia
Teva Investigational Site 166
🇺🇸Waukesha, Wisconsin, United States
Teva Investigational Site 557
🇨🇿Plzen, Czechia
Teva Investigational Site 504
🇩🇪Mainz, Germany
Teva Investigational Site 519
🇵🇱Bydgoszcz, Poland
Teva Investigational Site 502
🇩🇪Gera, Germany
Teva Investigational Site 540
ðŸ‡ðŸ‡ºBalassagyarmat, Hungary
Teva Investigational Site 541
ðŸ‡ðŸ‡ºBudapest, Hungary
Teva Investigational Site 545
ðŸ‡ðŸ‡ºKalocsa, Hungary
Teva Investigational Site 546
ðŸ‡ðŸ‡ºGyor, Hungary
Teva Investigational Site 514
🇵🇱Belchatow, Poland
Teva Investigational Site 539
ðŸ‡ðŸ‡ºDoba, Hungary
Teva Investigational Site 510
🇵🇱Bydgoszcz, Poland
Teva Investigational Site 536
🇵🇱Bydgoszcz, Poland
Teva Investigational Site 523
🇵🇱Chelmno, Poland
Teva Investigational Site 513
🇵🇱Gdansk, Poland
Teva Investigational Site 512
🇵🇱Katowice, Poland
Teva Investigational Site 552
🇵🇱Katowice, Poland
Teva Investigational Site 509
🇵🇱Krakow, Poland
Teva Investigational Site 508
🇵🇱Lodz, Poland
Teva Investigational Site 511
🇵🇱Lublin, Poland
Teva Investigational Site 528
🇸🇰Rimavska Sobota, Slovakia
Teva Investigational Site 527
🇸🇰Kosice, Slovakia
Teva Investigational Site 176
🇺🇸Loma Linda, California, United States
Teva Investigational Site 178
🇺🇸Lincoln, Nebraska, United States
Teva Investigational Site 175
🇺🇸Saint Louis, Missouri, United States
Teva Investigational Site 160
🇺🇸Irvine, California, United States
Teva Investigational Site 165
🇺🇸Decatur, Georgia, United States
Teva Investigational Site 169
🇺🇸San Rafael, California, United States
Teva Investigational Site 131
🇺🇸Chicago, Illinois, United States
Teva Investigational Site 149
🇺🇸Memphis, Tennessee, United States
Teva Investigational Site 155
🇺🇸Augusta, Georgia, United States
Teva Investigational Site 129
🇺🇸Englewood, Colorado, United States
Teva Investigational Site 128
🇺🇸Albuquerque, New Mexico, United States
Teva Investigational Site 146
🇺🇸Raleigh, North Carolina, United States
Teva Investigational Site 538
ðŸ‡ðŸ‡ºBudapest, Hungary
Teva Investigational Site 520
🇵🇱Krakow, Poland
Teva Investigational Site 524
🇵🇱Lublin, Poland
Teva Investigational Site 549
🇵🇱Olsztyn, Poland
Teva Investigational Site 139
🇺🇸New Haven, Connecticut, United States
Teva Investigational Site 117
🇺🇸Gainesville, Florida, United States
Teva Investigational Site 112
🇺🇸Orlando, Florida, United States
Teva Investigational Site 142
🇺🇸Kansas City, Missouri, United States
Teva Investigational Site 133
🇺🇸Charleston, South Carolina, United States