Persistence of Effect and Safety of Valbenazine for the Treatment of Tardive Dyskinesia

A Phase 4, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study to Evaluate the Persistence of Effect and Safety of Valbenazine for the Treatment of Tardive Dyskinesia

This is a Phase 4, randomized, double-blind, placebo-controlled study to evaluate the persistence of effect of valbenazine 40 mg and 80 mg.

Study Overview

• Status: Completed
• Conditions: Tardive Dyskinesia (TD)
• Intervention / Treatment: Drug: Valbenazine; Drug: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00926
    • Neurocrine Clinical Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Neurocrine Clinical Site
  • California
    • Anaheim, California, United States, 92805
      • Neurocrine Clinical Site
    • Anaheim, California, United States, 92804
      • Neurocrine Clinical Site
    • Costa Mesa, California, United States, 92627
      • Neurocrine Clinical Site
    • Escondido, California, United States, 92056
      • Neurocrine Clinical Site
    • Fountain Valley, California, United States, 92708
      • Neurocrine Clinical Site
    • Glendale, California, United States, 91206
      • Neurocrine Clinical Site
    • La Habra, California, United States, 90631
      • Neurocrine Clinical Site
    • Lemon Grove, California, United States, 91945
      • Neurocrine Clinical Site
    • Norwalk, California, United States, 90650
      • Neurocrine Clinical Site
    • San Bernardino, California, United States, 92408
      • Neurocrine Clinical Site
    • San Diego, California, United States, 92108
      • Neurocrine Clinical Site
    • Torrance, California, United States, 90502
      • Neurocrine Clinical Site
  • Colorado
    • Pueblo, Colorado, United States, 81003
      • Neurocrine Clinical Site
  • Florida
    • Hialeah, Florida, United States, 33012
      • Neurocrine Clinical Site
    • Hialeah, Florida, United States, 33013
      • Neurocrine Clinical Site
    • Hialeah, Florida, United States, 33018
      • Neurocrine Clinical Site
    • Miami, Florida, United States, 33183
      • Neurocrine Clinical Site
    • North Miami, Florida, United States, 33161
      • Neurocrine Clinical Site
    • Orlando, Florida, United States, 32803
      • Neurocrine Clinical Site
  • Indiana
    • South Bend, Indiana, United States, 46601
      • Neurocrine Clinical Site
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • Neurocrine Clinical Site
    • East Lansing, Michigan, United States, 48824
      • Neurocrine Clinical Site
    • Grand Rapids, Michigan, United States, 49503
      • Neurocrine Clinical Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Neurocrine Clinical Site
    • Saint Louis, Missouri, United States, 63109
      • Neurocrine Clinical Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Neurocrine Clinical Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Neurocrine Clinical Site
  • New York
    • New York, New York, United States, 10029
      • Neurocrine Clinical Site
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Neurocrine Clinical Site
    • Mason, Ohio, United States, 45040
      • Neurocrine Clinical Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Neurocrine Clinical Site
  • Pennsylvania
    • Conshohocken, Pennsylvania, United States, 19428
      • Neurocrine Clinical Site
    • Scranton, Pennsylvania, United States, 18503
      • Neurocrine Clinical Site
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Neurocrine Clinical Site
  • Texas
    • DeSoto, Texas, United States, 75115
      • Neurocrine Clinical Site
    • Houston, Texas, United States, 77058
      • Neurocrine Clinical Site
    • Houston, Texas, United States, 44030
      • Neurocrine Clinical Site
    • Irving, Texas, United States, 75062
      • Neurocrine Clinical Site
    • Richmond, Texas, United States, 77407
      • Neurocrine Clinical Site
  • Virginia
    • Petersburg, Virginia, United States, 23805
      • Neurocrine Clinical Site
  • Washington
    • Spokane, Washington, United States, 99202
      • Neurocrine Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Have one of the following clinical diagnoses for at least 3 months before screening: Schizophrenia, Schizoaffective Disorder, or Mood Disorder
3. Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months before screening.
4. Be on stable doses if using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder. Subjects with bipolar disorder must be on stable doses of a mood stabilizer.
5. Be in general good health.
6. Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.

Exclusion Criteria:

1. Have an active, clinically significant unstable medical condition within 1 month before screening.
2. Have a known history of substance (drug) dependence, or substance or alcohol abuse.
3. Have a significant risk of suicidal or violent behavior.
4. Have been hospitalized for psychiatric disorder within 6 months before Day 1.
5. Have a known history of neuroleptic malignant syndrome.
6. Have a known history of long QT syndrome or cardiac arrhythmia.
7. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed).
8. Are currently taking tetrabenazine or deutetrabenazine, or have used valbenazine (INGREZA) within 30 days of screening.
9. Have received an investigational drug within 30 days before Day 1 or plan to use an investigational drug (other than NBI-98854) during the study.
10. Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline.
11. Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors (eg, tetrabenazine, deutetrabenazine).
12. Are currently pregnant or breastfeeding.
13. Have HIV or hepatitis B.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Valbenazine; vesicular monoamine transporter 2 (VMAT2) inhibitor; Other Names: Ingrezza, NBI-98854
Placebo Comparator: 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.	Drug: Placebo oral capsule; non-active dosage form
Experimental: 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.	Drug: Valbenazine; vesicular monoamine transporter 2 (VMAT2) inhibitor; Other Names: Ingrezza, NBI-98854

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences
• Investigators: Study Director: Chief Medical Officer, Chief Medical Officer

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2019
• Primary Completion (Actual): December 23, 2019
• Study Completion (Actual): January 30, 2020

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Actual): April 20, 2021
• Last Update Submitted That Met QC Criteria: March 28, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesia, Drug-Induced; Dyskinesias; Tardive Dyskinesia
• Other Study ID Numbers: NBI-98854-TD4002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No