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The Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine

Primary Purpose

Tardive Dyskinesia (TD)

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Valbenazine
Placebo oral capsule
Sponsored by
Neurocrine Biosciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tardive Dyskinesia (TD)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 a known history of neuroleptic malignant syndrome.
  5. Have a known history of long QT syndrome or cardiac arrhythmia.
  6. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed).
  7. Have ever taken valbenazine (INGREZZA or NBI-98854) or participated in a valbenazine clinical study.
  8. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study.
  9. Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline.
  10. Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors (eg, tetrabenazine, deutetrabenazine).
  11. Are currently pregnant or breastfeeding.
  12. Have HIV or hepatitis B.

Sites / Locations

  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site
  • Neurocrine Clinical Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Valbenazine

Placebo

Arm Description

Valbenazine or placebo oral capsules administered once daily for 7 weeks.

Placebo oral capsules administered once daily for 7 weeks.

Outcomes

Primary Outcome Measures

Participants With Withdrawal-Emergent Adverse Events
A withdrawal-emergent adverse event is an adverse event that begins during the Withdrawal Period.

Secondary Outcome Measures

Participants Who Experience Worsening of Symptoms as Measured by the Physician Withdrawal Checklist-20 (PWC-20)
The PWC-20 is a validated 20-item physician-rated survey that assesses the severity of potential symptoms of withdrawal. Items are rated on a scale from 0 to 3, with total scores ranging from 0 to 60. Worsening of symptoms is defined by 5 new symptoms of moderate or severe degree or a worsening of symptoms by 2 points on the PWC-20 scale during Weeks 5 to 7 compared with Week 4. Note: a 2-point worsening from 0 (none) at Week 4 to 2 (moderate) post-Week 4 is counted as a worsening of symptoms.
Absolute Worst Total Score as Measured by the Physician Withdrawal Checklist-20 (PWC-20)
The PWC-20 is a validated 20-item physician-rated survey that assesses the severity of potential symptoms of withdrawal. Items are rated on a scale from 0 to 3, with total scores ranging from 0 to 60. Larger values indicate more severe symptoms. Rickels et al (J Clin Psychopharmacol 2008) cites PWC-20 mean scores associated with withdrawal in the range of 15 to 24.
Severity of Withdrawal Symptoms as Measured by the Change From Withdrawal Baseline (Week 4) to Week 7 in the Modified Cocaine Selective Severity Assessment (mCSSA)
The mCSSA is an 18-item survey based on symptoms commonly associated with early cocaine abstinence, including depression, fatigue, anhedonia, anxiety, irritability, sleep disturbance, and inability to concentrate. Items are rated on scales of 0 to 7 or 0 to 8, with separate scale descriptions for each item. Larger values indicate more severe symptoms. The scale has been modified to be specific to study drug (valbenazine or placebo) instead of cocaine.
Overall Improvement From Baseline of TD Symptoms as Measured by the Clinical Global Impression-Tardive Dyskinesia-Improvement (CGI-TD-I) Score
The CGI-TD-I scale is a 7-point scale (range; 1=very much improved to 7=very much worse) used to assess overall improvement in TD symptoms since the initiation of study drug dosing.
Change in Severity of TD Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Tardive Dyskinesia-Severity (CGI-TD-S) Scale
The CGI-TD-S scale is a 7-point scale (range; 1=normal, not at all ill to 7=among the most extremely ill patient) used to assess the overall global severity of TD.

Full Information

First Posted
October 4, 2018
Last Updated
May 27, 2020
Sponsor
Neurocrine Biosciences
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1. Study Identification

Unique Protocol Identification Number
NCT03698331
Brief Title
The Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine
Official Title
A Phase 4, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
September 14, 2018 (Actual)
Primary Completion Date
April 3, 2019 (Actual)
Study Completion Date
April 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neurocrine Biosciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 4, randomized, double-blind, placebo-controlled study to evaluate the potential for clinical dependence and withdrawal symptoms associated with valbenazine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tardive Dyskinesia (TD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
89 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Valbenazine
Arm Type
Experimental
Arm Description
Valbenazine or placebo oral capsules administered once daily for 7 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo oral capsules administered once daily for 7 weeks.
Intervention Type
Drug
Intervention Name(s)
Valbenazine
Other Intervention Name(s)
Ingrezza, NBI-98854
Intervention Description
vesicular monoamine transporter 2 (VMAT2) inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
non-active dosage form
Primary Outcome Measure Information:
Title
Participants With Withdrawal-Emergent Adverse Events
Description
A withdrawal-emergent adverse event is an adverse event that begins during the Withdrawal Period.
Time Frame
3 weeks
Secondary Outcome Measure Information:
Title
Participants Who Experience Worsening of Symptoms as Measured by the Physician Withdrawal Checklist-20 (PWC-20)
Description
The PWC-20 is a validated 20-item physician-rated survey that assesses the severity of potential symptoms of withdrawal. Items are rated on a scale from 0 to 3, with total scores ranging from 0 to 60. Worsening of symptoms is defined by 5 new symptoms of moderate or severe degree or a worsening of symptoms by 2 points on the PWC-20 scale during Weeks 5 to 7 compared with Week 4. Note: a 2-point worsening from 0 (none) at Week 4 to 2 (moderate) post-Week 4 is counted as a worsening of symptoms.
Time Frame
3 weeks
Title
Absolute Worst Total Score as Measured by the Physician Withdrawal Checklist-20 (PWC-20)
Description
The PWC-20 is a validated 20-item physician-rated survey that assesses the severity of potential symptoms of withdrawal. Items are rated on a scale from 0 to 3, with total scores ranging from 0 to 60. Larger values indicate more severe symptoms. Rickels et al (J Clin Psychopharmacol 2008) cites PWC-20 mean scores associated with withdrawal in the range of 15 to 24.
Time Frame
3 weeks
Title
Severity of Withdrawal Symptoms as Measured by the Change From Withdrawal Baseline (Week 4) to Week 7 in the Modified Cocaine Selective Severity Assessment (mCSSA)
Description
The mCSSA is an 18-item survey based on symptoms commonly associated with early cocaine abstinence, including depression, fatigue, anhedonia, anxiety, irritability, sleep disturbance, and inability to concentrate. Items are rated on scales of 0 to 7 or 0 to 8, with separate scale descriptions for each item. Larger values indicate more severe symptoms. The scale has been modified to be specific to study drug (valbenazine or placebo) instead of cocaine.
Time Frame
7 weeks
Title
Overall Improvement From Baseline of TD Symptoms as Measured by the Clinical Global Impression-Tardive Dyskinesia-Improvement (CGI-TD-I) Score
Description
The CGI-TD-I scale is a 7-point scale (range; 1=very much improved to 7=very much worse) used to assess overall improvement in TD symptoms since the initiation of study drug dosing.
Time Frame
Baseline, Week 4, Week 7
Title
Change in Severity of TD Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Tardive Dyskinesia-Severity (CGI-TD-S) Scale
Description
The CGI-TD-S scale is a 7-point scale (range; 1=normal, not at all ill to 7=among the most extremely ill patient) used to assess the overall global severity of TD.
Time Frame
Baseline, Week 4, Week 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. Have one of the following clinical diagnoses for at least 3 months before screening: Schizophrenia, Schizoaffective Disorder, or Mood Disorder Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months before screening. 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. 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 before screening. Have a known history of substance (drug) dependence, or substance 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 ever taken valbenazine (INGREZZA or NBI-98854) or participated in a valbenazine clinical study. 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 a blood loss ≥550 mL or donated blood within 30 days prior to Baseline. Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors (eg, tetrabenazine, deutetrabenazine). Are currently pregnant or breastfeeding. Have HIV or hepatitis B.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Medical Officer
Organizational Affiliation
Chief Medical Officer
Official's Role
Study Director
Facility Information:
Facility Name
Neurocrine Clinical Site
City
Anaheim
State/Province
California
ZIP/Postal Code
92804
Country
United States
Facility Name
Neurocrine Clinical Site
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States
Facility Name
Neurocrine Clinical Site
City
Norwalk
State/Province
California
ZIP/Postal Code
90650
Country
United States
Facility Name
Neurocrine Clinical Site
City
Oceanside
State/Province
California
ZIP/Postal Code
92054
Country
United States
Facility Name
Neurocrine Clinical Site
City
San Bernardino
State/Province
California
ZIP/Postal Code
92108
Country
United States
Facility Name
Neurocrine Clinical Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Neurocrine Clinical Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33013
Country
United States
Facility Name
Neurocrine Clinical Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33018
Country
United States
Facility Name
Neurocrine Clinical Site
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
Neurocrine Clinical Site
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
Facility Name
Neurocrine Clinical Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Neurocrine Clinical Site
City
Beechwood
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
Neurocrine Clinical Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Neurocrine Clinical Site
City
Scranton
State/Province
Pennsylvania
ZIP/Postal Code
18503
Country
United States
Facility Name
Neurocrine Clinical Site
City
DeSoto
State/Province
Texas
ZIP/Postal Code
75115
Country
United States
Facility Name
Neurocrine Clinical Site
City
Irving
State/Province
Texas
ZIP/Postal Code
75062
Country
United States
Facility Name
Neurocrine Clinical Site
City
San Juan
ZIP/Postal Code
00926
Country
Puerto Rico

12. IPD Sharing Statement

Plan to Share IPD
No

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The Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine

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