Tardive Dyskinesia
Conditions
Brief summary
This Phase 3b, rollover study will provide participants who completed a Phase 3 valbenazine (NBI-98854) study open-label access to valbenazine (fixed doses administered once daily) for the treatment of adults with TD until valbenazine is anticipated to be available commercially or they complete 72 weeks of treatment. This study will allow enrollment of up to 150 medically stable male and female participants with TD who previously participated in and completed the NBI-98854-1304 (Kinect 3) or NBI-98854-1402 (Kinect 4) Phase 3 study.
Detailed description
This study was terminated after 60 weeks due to the commercial availability of valbenazine.
Interventions
DRUGValbenazine
Sponsors
Neurocrine Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Have participated in and completed the NBI-98854-1304 (Kinect 3) or NBI-98854-1402 (Kinect 4) Phase 3 study. * Participants of childbearing potential must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently throughout the study and until 30 days after the last dose of valbenazine. * If using maintenance medication(s) for schizophrenia or schizoaffective disorder, mood disorder, or other conditions, be on stable doses. * Be in general good health. * Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
Exclusion criteria
* Have an active, clinically significant unstable medical condition within 1 month prior to screening. * Have a known history of substance dependence, substance (drug) or alcohol abuse. * Have a significant risk of suicidal or violent behavior. * Have a known history of neuroleptic malignant syndrome. * Have a known history of long QT syndrome or cardiac arrhythmia. * Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed). * Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than valbenazine) during the study. * Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline. * Have an allergy, hypersensitivity, or intolerance to tetrabenazine. * Are currently pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Monitored for Long-term Safety of Valbenazine | 60 weeks | Incidence of adverse events and monitoring of vital signs, clinical laboratory values, and electrocardiograms. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). Summaries of the incidence of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Baseline and Weeks 12, 24, 36, 48, and 60 | Clinician's perspective of the participant's overall severity of TD symptoms. The CGI-TD-Severity is based on a 7-point scale (range: 1= Normal, not at all ill to 7= Among the most extremely ill patient). A clinical response was defined as a CGI-TD-S score equal to 1 or 2. |
| Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Baseline and Weeks 12, 24, 36, 48, and 60 | Participant's perspective of his/her satisfaction with valbenazine treatment. The PSQ is based on a 5-point scale (range: 1=very satisfied to 5=very dissatisfied). A clinical response was defined as a PSQ score equal to 1 or 2. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valbenazine 40 mg Participants received 40 mg valbenazine oral capsule once daily for up to 60 weeks. | 35 |
| Valbenazine 80 mg Participants received 40 mg valbenazine oral capsule once daily for 4 weeks, followed by 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily for up to 56 weeks | 117 |
| Valbenazine 40/80 mg Participants received 40 mg valbenazine oral capsule once daily for 4 weeks. Participants were then increased to 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily, and due to poor tolerance, were subsequently reduced back to one 40 mg valbenazine oral capsule once daily for the remainder of the study, up to 56 weeks | 8 |
| Total | 160 |
Baseline characteristics
| Characteristic | Total | Valbenazine 40 mg | Valbenazine 80 mg | Valbenazine 40/80 mg |
|---|---|---|---|---|
| Age at Diagnosis Mood Disorder | 34.7 years STANDARD_DEVIATION 1.8 | 36.0 years STANDARD_DEVIATION 3.6 | 33.9 years STANDARD_DEVIATION 2.1 | 46.0 years STANDARD_DEVIATION 14 |
| Age at Diagnosis Schizophrenia/Schizoaffective Disorder | 28.2 years STANDARD_DEVIATION 10.6 | 27.1 years STANDARD_DEVIATION 8.3 | 28.7 years STANDARD_DEVIATION 11.4 | 25.3 years STANDARD_DEVIATION 6.2 |
| Age at Diagnosis Tardive Dyskinesia | 48.0 years STANDARD_DEVIATION 10.1 | 48.3 years STANDARD_DEVIATION 11.2 | 48.4 years STANDARD_DEVIATION 9.5 | 43.8 years STANDARD_DEVIATION 13.7 |
| Age, Continuous | 57.9 years STANDARD_DEVIATION 8.8 | 57.3 years STANDARD_DEVIATION 8.9 | 57.9 years STANDARD_DEVIATION 8.8 | 59.3 years STANDARD_DEVIATION 9 |
| Body Mass Index (BMI) at Baseline | 28.77 kg/m^2 STANDARD_DEVIATION 5.46 | 29.15 kg/m^2 STANDARD_DEVIATION 5.52 | 28.54 kg/m^2 STANDARD_DEVIATION 5.48 | 30.55 kg/m^2 STANDARD_DEVIATION 5.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 57 Participants | 4 Participants | 52 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 103 Participants | 31 Participants | 65 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Primary Psychiatric Diagnosis Mood disorder | 56 Participants | 12 Participants | 42 Participants | 2 Participants |
| Primary Psychiatric Diagnosis Schizophrenia/schizoaffective disorder | 104 Participants | 23 Participants | 75 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 14 Participants | 30 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 111 Participants | 21 Participants | 86 Participants | 4 Participants |
| Scales BPRS Score | 26.6 units on a scale STANDARD_DEVIATION 6 | 27.3 units on a scale STANDARD_DEVIATION 6.3 | 26.1 units on a scale STANDARD_DEVIATION 5.6 | 30.5 units on a scale STANDARD_DEVIATION 9.2 |
| Scales CGI-TD-Severity Score | 3.9 units on a scale STANDARD_DEVIATION 1.2 | 3.9 units on a scale STANDARD_DEVIATION 1.1 | 3.9 units on a scale STANDARD_DEVIATION 1.3 | 4.3 units on a scale STANDARD_DEVIATION 0.7 |
| Sex: Female, Male Female | 79 Participants | 22 Participants | 54 Participants | 3 Participants |
| Sex: Female, Male Male | 81 Participants | 13 Participants | 63 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 3 / 117 | 1 / 8 |
| other Total, other adverse events | 6 / 35 | 23 / 117 | 6 / 8 |
| serious Total, serious adverse events | 3 / 35 | 11 / 117 | 2 / 8 |
Outcome results
Primary
Number of Participants Monitored for Long-term Safety of Valbenazine
Incidence of adverse events and monitoring of vital signs, clinical laboratory values, and electrocardiograms. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). Summaries of the incidence of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared.
Time frame: 60 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valbenazine 40 mg | Number of Participants Monitored for Long-term Safety of Valbenazine | 35 Participants |
| Valbenazine 80 mg | Number of Participants Monitored for Long-term Safety of Valbenazine | 117 Participants |
| Valbenazine 40/80 mg | Number of Participants Monitored for Long-term Safety of Valbenazine | 8 Participants |
Secondary
Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale
Clinician's perspective of the participant's overall severity of TD symptoms. The CGI-TD-Severity is based on a 7-point scale (range: 1= Normal, not at all ill to 7= Among the most extremely ill patient). A clinical response was defined as a CGI-TD-S score equal to 1 or 2.
Time frame: Baseline and Weeks 12, 24, 36, 48, and 60
Population: Safety analysis set: includes all participants who were enrolled in the study and received study drug, with the following two exclusions: (a) participants who withdrew from the study and returned all previously dispensed study drug with all doses present, and (b) participants who had no post-baseline data collected.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 24 | 11 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 48 | 5 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 12 | 15 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 60 | 2 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 36 | 7 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Baseline | 2 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 12 | 56 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 36 | 44 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 24 | 56 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Baseline | 21 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 48 | 29 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 60 | 2 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 48 | 2 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 12 | 3 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 24 | 4 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Baseline | 0 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale | Week 36 | 2 Participants |
Secondary
Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ)
Participant's perspective of his/her satisfaction with valbenazine treatment. The PSQ is based on a 5-point scale (range: 1=very satisfied to 5=very dissatisfied). A clinical response was defined as a PSQ score equal to 1 or 2.
Time frame: Baseline and Weeks 12, 24, 36, 48, and 60
Population: Safety analysis set: includes all participants who were enrolled in the study and received study drug, with the following two exclusions: (a) participants who withdrew from the study and returned all previously dispensed study drug with all doses present, and (b) participants who had no post-baseline data collected.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 24 | 23 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Baseline | 35 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 36 | 17 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 12 | 30 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 48 | 12 Participants |
| Valbenazine 40 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 60 | 2 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 48 | 38 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 24 | 92 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 60 | 2 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Baseline | 116 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 12 | 112 Participants |
| Valbenazine 80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 36 | 66 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 12 | 6 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 24 | 6 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 36 | 5 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Baseline | 7 Participants |
| Valbenazine 40/80 mg | Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) | Week 48 | 5 Participants |