The Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine

Tardive Dyskinesia (TD) Clinical Trial

Official title:

A Phase 4, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03698331
• Other study ID #: NBI-98854-TD4001
• Status: Completed
• Phase: Phase 4
• Start date: September 14, 2018
• Est. completion date: April 3, 2019

Study information

• Verified date: May 2020
• Source: Neurocrine Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: April 3, 2019
• Est. primary completion date: April 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dyskinesias
• Substance Withdrawal Syndrome
• Tardive Dyskinesia
• Tardive Dyskinesia (TD)

Intervention

Drug:
• Valbenazine
vesicular monoamine transporter 2 (VMAT2) inhibitor
• Placebo oral capsule
non-active dosage form

Locations

Country	Name	City	State
Puerto Rico	Neurocrine Clinical Site	San Juan
United States	Neurocrine Clinical Site	Anaheim	California
United States	Neurocrine Clinical Site	Ann Arbor	Michigan
United States	Neurocrine Clinical Site	Beechwood	Ohio
United States	Neurocrine Clinical Site	DeSoto	Texas
United States	Neurocrine Clinical Site	Fort Wayne	Indiana
United States	Neurocrine Clinical Site	Glendale	California
United States	Neurocrine Clinical Site	Hialeah	Florida
United States	Neurocrine Clinical Site	Hialeah	Florida
United States	Neurocrine Clinical Site	Hialeah	Florida
United States	Neurocrine Clinical Site	Honolulu	Hawaii
United States	Neurocrine Clinical Site	Irving	Texas
United States	Neurocrine Clinical Site	Norwalk	California
United States	Neurocrine Clinical Site	Oceanside	California
United States	Neurocrine Clinical Site	Oklahoma City	Oklahoma
United States	Neurocrine Clinical Site	San Bernardino	California
United States	Neurocrine Clinical Site	Scranton	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Neurocrine Biosciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants With Withdrawal-Emergent Adverse Events	A withdrawal-emergent adverse event is an adverse event that begins during the Withdrawal Period.	3 weeks
Secondary	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.	3 weeks
Secondary	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.	3 weeks
Secondary	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.	7 weeks
Secondary	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.	Baseline, Week 4, Week 7
Secondary	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.	Baseline, Week 4, Week 7