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This is a Phase 4, randomized, double-blind, placebo-controlled study to evaluate the persistence of effect of valbenazine 40 mg and 80 mg.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open-label Valbenazine | Experimental | Participants received valbenazine 40 mg once daily for 1 week, then 80 mg once daily for the remainder of the 8-week open label period. |
|
| Placebo-controlled Placebo | Placebo Comparator | Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. |
|
| Placebo-controlled Valbenazine | Experimental | Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Valbenazine | Drug | vesicular monoamine transporter 2 (VMAT2) inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Randomization (Week 8) in Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score at Week 16 | The AIMS rates 10 items of involuntary movement, each item ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Items assess facial, oral, extremity, and trunk movements, as well as self-awareness of abnormal movements. The AIMS Dyskinesia Total Score is the sum of items 1-7 and ranges from 0 to 28, with higher scores indicating more severe dyskinesia. Least-squares mean were estimated using a mixed-effects model for repeated measures. | Week 8, Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Health State Index Score at Week 16 | The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The health state index score is based on the results of the individual health profiles using the United States value set and ranges from -0.573 to 1.0, with higher scores indicating higher health utility. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Chief Medical Officer | Chief Medical Officer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Neurocrine Clinical Site | Little Rock | Arkansas | 72211 | United States | ||
| Neurocrine Clinical Site |
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After receiving valbenazine 40 mg for the first week followed by valbenazine 80 mg for 7 weeks during the open-label period, participants were randomly assigned to either placebo or to continue to receive valbenazine 80 mg.
The study enrolled male and female participants, 18 to 85 years of age, from 28 centers in the United States. Participants must have clinical diagnoses of schizophrenia or schizoaffective disorder with neuroleptic-induced tardive dyskinesia (TD) or mood disorder with neuroleptic-induced TD and have moderate or severe TD as assessed by an external Abnormal Involuntary Movement Scale (AIMS) Reviewer. The first and last participant was enrolled on 18 March 2019 and 3 September 2019, respectively.
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| ID | Title | Description |
|---|---|---|
| FG000 | Open-label Valbenazine | Participants received valbenazine 40 mg once daily for 1 week, then 80 mg once daily for the remainder of the 8-week open label period. |
| FG001 | Placebo-controlled Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Open-label Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 14, 2019 | Feb 16, 2021 |
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| Placebo oral capsule | Drug | non-active dosage form |
|
| Baseline, Week 16 |
| Change From Baseline in the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) at Week 16 | The EQ-5D-5L assesses general health-related quality of life. The second portion of the scale is a self-perceived health score assessed using a VAS that ranges from 0 ("the worst imaginable health") to 100 ("the best imaginable health"). | Baseline, Week 16 |
| Anaheim |
| California |
| 92804 |
| United States |
| Neurocrine Clinical Site | Anaheim | California | 92805 | United States |
| Neurocrine Clinical Site | Costa Mesa | California | 92627 | United States |
| Neurocrine Clinical Site | Escondido | California | 92056 | United States |
| Neurocrine Clinical Site | Fountain Valley | California | 92708 | United States |
| Neurocrine Clinical Site | Glendale | California | 91206 | United States |
| Neurocrine Clinical Site | La Habra | California | 90631 | United States |
| Neurocrine Clinical Site | Lemon Grove | California | 91945 | United States |
| Neurocrine Clinical Site | Norwalk | California | 90650 | United States |
| Neurocrine Clinical Site | San Bernardino | California | 92408 | United States |
| Neurocrine Clinical Site | San Diego | California | 92108 | United States |
| Neurocrine Clinical Site | Torrance | California | 90502 | United States |
| Neurocrine Clinical Site | Pueblo | Colorado | 81003 | United States |
| Neurocrine Clinical Site | Hialeah | Florida | 33012 | United States |
| Neurocrine Clinical Site | Hialeah | Florida | 33013 | United States |
| Neurocrine Clinical Site | Hialeah | Florida | 33018 | United States |
| Neurocrine Clinical Site | Miami | Florida | 33183 | United States |
| Neurocrine Clinical Site | North Miami | Florida | 33161 | United States |
| Neurocrine Clinical Site | Orlando | Florida | 32803 | United States |
| Neurocrine Clinical Site | South Bend | Indiana | 46601 | United States |
| Neurocrine Clinical Site | Bloomfield Hills | Michigan | 48302 | United States |
| Neurocrine Clinical Site | East Lansing | Michigan | 48824 | United States |
| Neurocrine Clinical Site | Grand Rapids | Michigan | 49503 | United States |
| Neurocrine Clinical Site | Kansas City | Missouri | 64108 | United States |
| Neurocrine Clinical Site | St Louis | Missouri | 63109 | United States |
| Neurocrine Clinical Site | Lincoln | Nebraska | 68526 | United States |
| Neurocrine Clinical Site | Las Vegas | Nevada | 89102 | United States |
| Neurocrine Clinical Site | New York | New York | 10029 | United States |
| Neurocrine Clinical Site | Beachwood | Ohio | 44122 | United States |
| Neurocrine Clinical Site | Mason | Ohio | 45040 | United States |
| Neurocrine Clinical Site | Oklahoma City | Oklahoma | 73112 | United States |
| Neurocrine Clinical Site | Conshohocken | Pennsylvania | 19428 | United States |
| Neurocrine Clinical Site | Scranton | Pennsylvania | 18503 | United States |
| Neurocrine Clinical Site | Franklin | Tennessee | 37067 | United States |
| Neurocrine Clinical Site | DeSoto | Texas | 75115 | United States |
| Neurocrine Clinical Site | Houston | Texas | 44030 | United States |
| Neurocrine Clinical Site | Houston | Texas | 77058 | United States |
| Neurocrine Clinical Site | Irving | Texas | 75062 | United States |
| Neurocrine Clinical Site | Richmond | Texas | 77407 | United States |
| Neurocrine Clinical Site | Petersburg | Virginia | 23805 | United States |
| Neurocrine Clinical Site | Spokane | Washington | 99202 | United States |
| Neurocrine Clinical Site | San Juan | PR | 00926 | Puerto Rico |
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
| FG002 | Placebo-controlled Valbenazine | Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. |
| Safety Analysis Set | The safety analysis set for the open-label valbenazine group in this period includes all participants who received at least one dose of study drug and have any post-baseline safety data collected. |
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| COMPLETED |
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| NOT COMPLETED |
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| Placebo-controlled Period and Follow-up |
|
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Persistence of effect analysis set, which includes all randomized participants who received at least one dose of randomized study drug and have at least one AIMS assessment during the placebo-controlled period.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo-controlled Placebo | Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. |
| BG001 | Placebo-controlled Valbenazine | Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Abnormal Involuntary Movement Scale at Study Baseline | The Abnormal Involuntary Movement Scale (AIMS) rates 10 items of involuntary movement, each item ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Items assess facial, oral, extremity, and trunk movements, as well as self-awareness of abnormal movements. The AIMS Dyskinesia Total Score is the sum of items 1-7 and ranges from 0 to 28, with higher scores indicating more severe dyskinesia. | Mean | Standard Deviation | Score on scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Randomization (Week 8) in Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score at Week 16 | The AIMS rates 10 items of involuntary movement, each item ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Items assess facial, oral, extremity, and trunk movements, as well as self-awareness of abnormal movements. The AIMS Dyskinesia Total Score is the sum of items 1-7 and ranges from 0 to 28, with higher scores indicating more severe dyskinesia. Least-squares mean were estimated using a mixed-effects model for repeated measures. | Persistence of effect analysis set, which includes all randomized participants who received at least one dose of randomized study drug and have at least one AIMS assessment during the placebo-controlled period. Participants who do not have an AIMS assessment at a scheduled or mapped early termination visit are not included in the analysis. | Posted | Least Squares Mean | 95% Confidence Interval | Score on scale | Week 8, Week 16 |
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| ||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Health State Index Score at Week 16 | The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The health state index score is based on the results of the individual health profiles using the United States value set and ranges from -0.573 to 1.0, with higher scores indicating higher health utility. | Includes all participants who received at least one dose of study drug and have at least one postbaseline assessment. Missing data were imputed with last observation carried forward. | Posted | Mean | Standard Error | Score on scale | Baseline, Week 16 |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) at Week 16 | The EQ-5D-5L assesses general health-related quality of life. The second portion of the scale is a self-perceived health score assessed using a VAS that ranges from 0 ("the worst imaginable health") to 100 ("the best imaginable health"). | Includes all participants who received at least one dose of study drug and have at least one postbaseline assessment. Missing data were imputed with last observation carried forward. | Posted | Mean | Standard Error | Score on scale | Baseline, Week 16 |
|
|
Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open-label Valbenazine | Participants received valbenazine 40 mg once daily for 1 week, then 80 mg once daily for the remainder of the 8-week open label period. | 1 | 132 | 3 | 132 | 17 | 132 |
| EG001 | Placebo-controlled Placebo | Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. | 0 | 59 | 2 | 59 | 11 | 59 |
| EG002 | Placebo-controlled Valbenazine | Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. | 0 | 59 | 1 | 59 | 7 | 59 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Psychotic disorder | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Knee arthroplasty | Surgical and medical procedures | MedDRA (21.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (21.0) | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA (21.0) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (21.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
|
Generally, the PI has the right to publish results provided such publication does not violate confidentiality or IP provisions within the contract with the Sponsor. Prior to submission for publication or presentation of results, the PI must provide the Sponsor time for review. The Sponsor can request the PI to withhold or remove information from all publications. For a multi-center study, any publication of results by the PI shall not be made before the first multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Neurocrine Medical Information | Neurocrine Biosciences | 877-641-3461 | medinfo@neurocrine.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 2, 2020 | Feb 16, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000071057 | Tardive Dyskinesia |
| ID | Term |
|---|---|
| D004409 | Dyskinesia, Drug-Induced |
| D020820 | Dyskinesias |
| D009069 | Movement Disorders |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000603978 | valbenazine |
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| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Units | Counts |
|---|---|
| Participants |
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