A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel, Fixed-Dose Study to Assess the Efficacy, Safety, and Tolerability of NBI-98854 for the Treatment of Tardive Dyskinesia
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Neurocrine Biosciences
- Enrollment
- 234
- Primary Endpoint
- Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
Study Overview
Brief Summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of NBI-98854 administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.
Detailed Description
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel, fixed-dose study to evaluate the efficacy, safety, and tolerability of two doses of NBI-98854 (40 mg and 80 mg) compared to placebo, administered once daily. The study design includes a double-blind, placebo-controlled treatment period for 6 weeks and a double-blind NBI-98854 treatment period for an additional 42 weeks, for a total of 48 weeks of treatment. Final follow-up assessments will be conducted 4 weeks after the last dose of the study drug.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study.
- •Female subjects must not be pregnant.
- •Have one of the following clinical diagnoses for at least 3 months prior to screening: Schizophrenia or Schizoaffective Disorder, or Mood Disorder.
- •Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months prior to screening.
- •Have moderate or severe TD.
- •If using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder, be on stable doses.
- •Be in good general health.
- •Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
- •Have a negative drug screen for amphetamines,barbiturates, benzodiazepines, phencyclidine, cocaine, opiates, or cannabinoids
Exclusion Criteria
- •Have an active, clinically significant unstable medical condition within 1 month prior to screening.
- •Have a known history of substance dependence, or 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 tachy-arrhythmia.
- •Have a cancer diagnosis within 3 years of screening (some exceptions allowed)
- •Have received an investigational drug within 30 days prior to screening or plan to use an investigational drug (other than NBI-98854) 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.
- •Have had previous exposure with NBI-98854 or had previously participated in an NBI-98854 clinical study.
- •Are currently pregnant or breastfeeding.
Arms & Interventions
NBI-98854 40 mg
NBI-98854 administered as one (1) 40 mg capsule and one (1) placebo capsule, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Intervention: NBI-98854 (Drug)
NBI-98854 40 mg
NBI-98854 administered as one (1) 40 mg capsule and one (1) placebo capsule, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Intervention: Placebo (Drug)
NBI-98854 80 mg
Subjects randomized to the NBI-98854 80 mg dose will receive NBI-98854 40 mg for the first week (administered as one (1) 40 mg capsule and one (1) placebo capsule), followed by NBI-98854 80 mg administered as two (2) 40 mg capsules, taken by mouth, every morning between 7:00am - 10:00am for 5 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Intervention: NBI-98854 (Drug)
NBI-98854 80 mg
Subjects randomized to the NBI-98854 80 mg dose will receive NBI-98854 40 mg for the first week (administered as one (1) 40 mg capsule and one (1) placebo capsule), followed by NBI-98854 80 mg administered as two (2) 40 mg capsules, taken by mouth, every morning between 7:00am - 10:00am for 5 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Intervention: Placebo (Drug)
Placebo
Placebo administered as two (2) placebo capsules, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and be randomized to either a 40 mg or 80 mg dose. Subjects re-randomized to receive NBI-98854 80 mg will receive 40 mg for the first week.
Intervention: NBI-98854 (Drug)
Placebo
Placebo administered as two (2) placebo capsules, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and be randomized to either a 40 mg or 80 mg dose. Subjects re-randomized to receive NBI-98854 80 mg will receive 40 mg for the first week.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
Time Frame: Baseline and Week 6
Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by blinded central AIMS video raters. The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity.
Secondary Outcomes
- Clinical Global Impression of Change - TD (CGI-TD) at Week 6(Week 6)
- Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Responder Analysis at Week 6(Week 6)