Valbenazine for Tardive Dyskinesia

Overseen By John M de Figueiredo,, MD, ScD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: CYP3A4 inducers, Dopamine agonists

Disqualifiers: Unstable psychiatric status, Cognitive impairment, Substance use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This will be an Investigator-initiated pilot study in which participants will be assessed with various scales to measure demoralization, anxiety, depression, and subjective incompetence at baseline and every two weeks after treatment with Valbenazine for a total of 6 weeks. Improvement in TD will be assessed as well and correlated with reduction in demoralization.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including strong CYP3A4 inducers, dopamine agonists, MAO inhibitors, stimulants, and VMAT2 inhibitors.

What data supports the effectiveness of the drug Valbenazine for treating tardive dyskinesia?

Valbenazine, the first FDA-approved drug for tardive dyskinesia, has shown significant improvement in symptoms during clinical trials, with a notable effect size at a dose of 80 mg/day. It is a modified version of another drug used for movement disorders and offers better dosing and side effect profiles. ^{1 2 3 4 5}

Is Valbenazine safe for humans?

Valbenazine has been shown to be safe in humans during clinical trials, with a good short-term side effect profile and effective once-a-day dosing. Long-term safety data is still being gathered, but it has been used safely in patients with tardive dyskinesia over extended periods. ^{1 2 5 6 7}

How is the drug Valbenazine unique for treating tardive dyskinesia?

Valbenazine is unique because it is the first FDA-approved drug specifically for tardive dyskinesia, working by selectively inhibiting VMAT2 (a protein involved in dopamine regulation), and it offers the convenience of once-a-day dosing with a better short-term side effect profile compared to similar treatments. ^{1 2 3 4 8}

Research Team

John De Figueiredo, MD

Principal Investigator

Clinical Professor of Psychiatry

Eligibility Criteria

This trial is for individuals aged 26-84 who have been diagnosed with tardive dyskinesia, a condition causing involuntary movements, as a result of taking neuroleptic medications. Both males and females are eligible if they meet the DSM-5 criteria for this condition.

Inclusion Criteria

I am between 26 and 84 years old.

My gender does not affect my eligibility.

I have involuntary movements due to medication for mental health.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Valbenazine and are assessed with various scales to measure demoralization, anxiety, depression, and subjective incompetence every two weeks

6 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Valbenazine

Trial Overview The study is testing whether Valbenazine can help reduce feelings of demoralization in patients with tardive dyskinesia by treating their symptoms. It's a preliminary step to see if it's worth doing larger studies on this potential treatment.

Participant Groups

Group I: Valbenazine Experimental Treatment 1 Intervention

All participants will be treated with Valbenazine for 6 weeks.

Valbenazine is already approved in United States for the following indications:

Approved in United States as Ingrezza for:

• Tardive dyskinesia
• Chorea associated with Huntington's disease

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Neurocrine Biosciences

Industry Sponsor

Trials

78

Recruited

6,600+

Kyle W. Gano

Neurocrine Biosciences

Chief Executive Officer since 2024

PhD in Pharmacology

Dr. Sanjay Keswani

Neurocrine Biosciences

Chief Medical Officer

MD

Findings from Research

Valbenazine (Ingrezza) is the first medication approved by the FDA specifically for treating tardive dyskinesia, a condition characterized by involuntary movements often caused by long-term use of antipsychotic medications.

This approval marks a significant advancement in the management of tardive dyskinesia, providing patients with a targeted treatment option to help alleviate their symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valbenazine (Ingrezza): The First FDA-Approved Treatment for Tardive Dyskinesia. Uhlyar, S., Rey, JA.[2020]

Valbenazine is the first FDA-approved medication specifically for treating tardive dyskinesia (TD), showing significant improvement in symptoms at a dose of 80 mg/day with a clinically meaningful effect size of 0.90 in short-term trials.

Compared to tetrabenazine, valbenazine offers advantages such as once-a-day dosing and a better short-term side effect profile, although further long-term studies are needed to fully understand its benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valbenazine for Tardive Dyskinesia. Freudenreich, O., Remington, G.[2022]

Valbenazine is a selective VMAT2 inhibitor that effectively modulates dopamine release, showing significant improvement in symptoms of tardive dyskinesia (TD) in clinical trials.

As there are currently no FDA-approved treatments for TD, valbenazine represents a promising new option, with a new drug application submitted for priority review in 2016.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valbenazine for the treatment of tardive dyskinesia. Barquero, N.[2017]

Valbenazine (Ingrezza™) is an approved treatment for tardive dyskinesia (TD) in adults, demonstrating its efficacy as a selective VMAT2 inhibitor for managing this condition.

The drug is also being explored for Tourette syndrome in phase 2 trials, indicating its potential for treating various central nervous system disorders beyond TD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valbenazine: First Global Approval. Kim, ES.[2018]

Valbenazine (VBZ) significantly improved tardive dyskinesia (TD) symptoms in subjects with mood disorders over a 48-week treatment period, with greater improvements observed at higher doses compared to placebo, indicating its efficacy as a treatment option.

After stopping VBZ treatment, TD symptoms began to return toward baseline levels, suggesting that while VBZ is effective in managing TD, ongoing treatment may be necessary to maintain symptom control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder. Correll, CU., Josiassen, RC., Liang, GS., et al.[2022]

Valbenazine, a VMAT2 inhibitor, is the first FDA-approved medication specifically for treating tardive dyskinesia (TD), showing effective results in a case study of a 49-year-old woman with severe TD symptoms.

In a phase III clinical trial, the once-daily dose of 80 mg of valbenazine was found to be both effective and safe for managing TD, even in a patient with a complex medical history and rapid onset of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Severe Tardive Dyskinesia with Valbenazine, Including a Patient's Perspective. Josiassen, RC., Filmyer, DM., Gillean, J., et al.[2019]

Valbenazine (VBZ) significantly improved tardive dyskinesia (TD) symptoms in subjects with schizophrenia or mood disorders over a treatment period of up to 48 weeks, with greater improvements observed at higher doses (80 mg) compared to placebo.

After stopping VBZ treatment, TD symptoms began to return toward baseline levels, indicating that while VBZ is effective for long-term management of TD, its effects diminish after discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder. Kane, JM., Correll, CU., Liang, GS., et al.[2022]

In a 6-week phase 3 trial involving 225 participants with moderate to severe tardive dyskinesia, valbenazine at 80 mg/day significantly reduced dyskinesia symptoms compared to placebo, with a mean change of -3.2 on the Abnormal Involuntary Movement Scale (AIMS).

Valbenazine was generally well tolerated, with a safety profile consistent with previous studies, and did not negatively impact psychiatric status, indicating its potential as a safe treatment option for tardive dyskinesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Hauser, RA., Factor, SA., Marder, SR., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Valbenazine (Ingrezza): The First FDA-Approved Treatment for Tardive Dyskinesia. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Valbenazine for Tardive Dyskinesia. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

Valbenazine for the treatment of tardive dyskinesia. [2017]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Valbenazine: First Global Approval. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Successful Treatment of Severe Tardive Dyskinesia with Valbenazine, Including a Patient's Perspective. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. [2022]