NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder (KINECT Study)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder

The purpose of this study is to evaluate the efficacy, safety, and tolerability of two doses (50 and 100 mg) of NBI-98854 administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.

Study Overview

• Status: Completed
• Conditions: Tardive Dyskinesia
• Intervention / Treatment: Drug: Placebo; Drug: NBI-98854; Drug: NBI-98854

Detailed Description

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety, and tolerability of two doses (50 and 100 mg) of NBI-98854 administered once daily for up to 2 weeks. The study will also allow for an evaluation of the efficacy of NBI-98854 50 mg once daily for up to 6 weeks and the safety and tolerability of NBI 98854 50 mg once daily for up to 12 weeks.

The double-blind placebo-controlled treatment period the study has three arms:

• NBI-98854 50 mg once daily for 6 weeks
• NBI-98854 100 mg once daily for 2 weeks followed by 50 mg once daily for the remaining 4 weeks
• placebo

At the end of the 6-week placebo-controlled double-blind treatment period, subjects will continue in the study for an additional 6-week open-label period where all subjects who have completed the double-blind treatment period will receive NBI-98854 50 mg once daily. Two and four weeks after the last dose of study drug, follow-up assessments will be performed.

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Caguas, Puerto Rico, 00725
  • San Juan, Puerto Rico, 00927
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
  • California
    • Anaheim, California, United States, 92804
    • Carson, California, United States, 90746
    • Colton, California, United States, 92324
    • Costa Mesa, California, United States, 92626
    • Downey, California, United States, 90241
    • Fountain Valley, California, United States, 92708
    • Glendale, California, United States, 91206
    • National City, California, United States, 91950
    • Oceanside, California, United States, 92056
    • Paramount, California, United States, 90723
    • San Bernardino, California, United States, 92408
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92108
    • San Diego, California, United States, 92123
    • San Diego, California, United States, 92121
    • Santa Ana, California, United States, 92705
  • Florida
    • Fort Lauderdale, Florida, United States, 33334
    • Hialeah, Florida, United States, 33012
    • Lauderhill, Florida, United States, 33319
    • Melbourne, Florida, United States, 32901
    • Miami Springs, Florida, United States, 33166
    • North Miami, Florida, United States, 33161
    • Orange City, Florida, United States, 32763
  • Georgia
    • Atlanta, Georgia, United States, 30342
  • Illinois
    • Chicago, Illinois, United States, 60612
    • Chicago, Illinois, United States, 60640
    • Schaumburg, Illinois, United States, 60194
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
    • Shreveport, Louisiana, United States, 71104
  • Maryland
    • Baltimore, Maryland, United States, 21285
    • Glen Burnie, Maryland, United States, 21061
  • Missouri
    • Saint Louis, Missouri, United States, 63141
    • Saint Louis, Missouri, United States, 63118
  • New Jersey
    • Toms River, New Jersey, United States, 08755
  • New York
    • Albany, New York, United States, 12208
    • Brooklyn, New York, United States, 11203
    • Wards Island, New York, United States, 10035
  • North Carolina
    • Hope Mills, North Carolina, United States, 28348
  • Ohio
    • Beachwood, Ohio, United States, 44122
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
  • Pennsylvania
    • Conshohocken, Pennsylvania, United States, 19428
  • South Carolina
    • Charleston, South Carolina, United States, 29407
  • Tennessee
    • Memphis, Tennessee, United States, 38119
  • Texas
    • DeSoto, Texas, United States, 75115
    • Irving, Texas, United States, 75062
  • Washington
    • Bothell, Washington, United States, 98011
    • Kirkland, Washington, United States, 98033
    • Spokane, Washington, United States, 99204

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:

• Have a clinical diagnosis of schizophrenia or schizoaffective disorder and a clinical diagnosis of neuroleptic-induced tardive dyskinesia for at least 3 months prior to screening.
• Be receiving a stable dose of antipsychotic medication for a minimum of 30 days before study start. Subjects who are not using antipsychotic medication must have stable psychiatric status.
• Have the doses of concurrent medications and the conditions being treated be stable for a minimum of 30 days before study start and be expected to remain stable during the study.
• Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal birth control during the study.
• Female subjects must not be pregnant.
• Be in good general health and expected to complete the clinical study as designed.
• Have a body mass index (BMI) of 18 to 38 kg/m2 (both inclusive).
• Have a negative urine drug screen (negative for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids) at screening and study start, except for any subject receiving a stable dose of benzodiazepine.
• Have a negative alcohol breath test at screening and study start.

Exclusion Criteria:

• Have an active clinically significant unstable medical condition within 1 month (30 days) prior to screening.
• Have a history of substance dependence or substance (drug) or alcohol abuse within the 3 months before study start(nicotine and caffeine dependence are not exclusionary).
• Have a known history of neuroleptic malignant syndrome.
• Have a significant risk of suicidal or violent behavior.
• Receiving any excluded concomitant medication such as reserpine, metoclopramide, stimulants, or tetrabenazine.
• Receiving medication for the treatment of tardive dyskinesia.
• Have a positive human immunodeficiency virus antibody, (HIV-Ab), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody result at screening or have a history of positive result.
• Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study.
• Have an allergy, hypersensitivity, or intolerance to tetrabenazine.
• Have had previous exposure with NBI-98854.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NBI-98854 50 mg; NBI-98854 50 mg administered as two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for 6 weeks.	Drug: NBI-98854; 25 mg capsule; Drug: NBI-98854; 50 mg capsule
Experimental: NBI-98854 100 mg and 50 mg; NBI-98854 100 mg administered as two (2) 50 mg capsules taken every morning between 7:00am - 10:00am for 2 weeks. After 2 weeks, NBI-98854 50 mg administered by two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for remaining 4 weeks.	Drug: NBI-98854; 25 mg capsule; Drug: NBI-98854; 50 mg capsule
Placebo Comparator: Placebo; Capsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6	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. The primary efficacy endpoint was the change from baseline in the AIMS dyskinesia total score at Week 6 between the pooled NBI-98854 50+100 mg group and placebo group analyzed using the ANCOVA model (LOCF, ITT analysis set).	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression - Global Improvement of TD (CGI-TD)	Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse). The ANOVA analysis of CGI-TD was conducted for the pooled NBI-98854 50+100 mg group and placebo group.	Week 6
Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 2	Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse).	Week 2

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences

Publications and helpful links

General Publications

• Sajatovic M, Alexopoulos GS, Burke J, Farahmand K, Siegert S. The effects of valbenazine on tardive dyskinesia in older and younger patients. Int J Geriatr Psychiatry. 2020 Jan;35(1):69-79. doi: 10.1002/gps.5218. Epub 2019 Oct 31.
• Josiassen RC, Kane JM, Liang GS, Burke J, O'Brien CF. Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. Psychopharmacol Bull. 2017 Aug 1;47(3):61-68.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: September 11, 2012
• First Submitted That Met QC Criteria: September 14, 2012
• First Posted (Estimate): September 19, 2012

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Movement Disorders; Dyskinesia, Drug-Induced; Schizophrenia; Psychotic Disorders; Dyskinesias; Tardive Dyskinesia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Tetrabenazine
• Other Study ID Numbers: NBI-98854-1201