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

A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Two-Period Cross-Over Study to Evaluate 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 (12.5 and 50 mg) of NBI-98854 administered once daily (q.d.) for the treatment of tardive dyskinesia in subjects with schizophrenia or schizoaffective disorder.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group, Inc
  • California
    • National City, California, United States, 91950
      • Synergy Clinical Research
    • San Diego, California, United States, 92108
      • PCSD - Feighner Research
    • San Diego, California, United States, 92103
      • UCSD Outpatient Psychiatry
  • Florida
    • Miami, Florida, United States, 33015
      • San Marcus Research Clinic, Inc.
    • Miami, Florida, United States, 33155
      • Medical Research Marseilles
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
  • Missouri
    • Saint Louis, Missouri, United States, 63118
      • St. Louis Clinical Trials
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 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 as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), 333.82 (see Appendix 17.1) 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 adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
• 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: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NBI-98854 12.5 mg; During the Cross-Over Study, subjects will be randomly assigned to receive one of the following treatment sequences: Sequence 1: Placebo once daily dose for Days 1-14 and 12.5 mg NBI-98854 once daily dose for Days 15-28. Sequence 2: 12.5 mg NBI-98854 once daily dose for Days 1-14 and placebo once daily dose for Days 15-28.	Drug: NBI-98854; 12.5 mg powder in bottle once daily for 14 days; Drug: NBI-98854; 50 mg powder in bottle once daily for 14 days; Drug: Placebo; Solution containing no active substance
Experimental: NBI-98854 50 mg; During the Cross-Over Study, subjects will be randomly assigned to receive one of the following treatment sequences: Sequence 3: Placebo once daily dose for Days 1-14 and 50 mg NBI-98854 once daily dose for Days 15-28. Sequence 4: 50 mg NBI-98854 once daily dose for Days 1-14 and placebo once daily dose for Days 15-28.	Drug: NBI-98854; 12.5 mg powder in bottle once daily for 14 days; Drug: NBI-98854; 50 mg powder in bottle once daily for 14 days; Drug: Placebo; Solution containing no active substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score	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.	Day 15 and 29, averaged

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).	Day 15 and 29, averaged

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences
• Investigators: Study Director: Christopher O'Brien, MD, Neurocrine Biosciences

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 13, 2011

Study Record Updates

• Last Update Posted (Actual): August 10, 2017
• Last Update Submitted That Met QC Criteria: July 14, 2017
• Last Verified: July 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-98854-1101