Deutetrabenazine for Huntington's Disease

Overseen By Amy E Brown, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Vanderbilt University Medical Center

Must not be taking: VMAT2 inhibitors

Disqualifiers: Severe depression, Suicidal ideation, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests deutetrabenazine, a medication, to determine if it can improve speech and movement problems in people with Huntington's Disease. The goal is to see if this treatment can ease daily life for those affected by the condition. Individuals diagnosed with Huntington's, who have noticeable movement issues and can walk at least 10 meters, may be suitable for this study. As a Phase 2/3 trial, the research measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering hope for improved daily living.

Will I have to stop taking my current medications?

The trial requires that you stop taking any current VMAT2 inhibitors (like tetrabenazine, deutetrabenazine, or valbenazine) before participating.

Is there any evidence suggesting that deutetrabenazine is likely to be safe for humans?

Research has shown that deutetrabenazine is generally well-tolerated by people with Huntington's disease. In previous studies, the number of people experiencing side effects was similar between those taking deutetrabenazine (64%) and those taking a placebo, or dummy pill (60%). This indicates that the treatment does not cause more side effects than a placebo.

However, some risks require attention. Deutetrabenazine can increase the risk of depression and thoughts of self-harm in people with Huntington's disease. It might also cause parkinsonism, leading to symptoms like muscle stiffness or tremors. These are important to consider because Huntington's disease itself can cause similar issues.

Overall, the safety profile of deutetrabenazine shows that while many people tolerate it well, some serious side effects can occur. Anyone considering participation in a trial should weigh these risks and consult with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Huntington's Disease?

Deutetrabenazine is unique because it offers a refined approach to managing Huntington's disease by specifically targeting chorea, a common and disruptive symptom. Unlike other treatments that may have broader effects, deutetrabenazine's mechanism focuses on modulating dopamine levels in the brain, which can lead to better chorea control with potentially fewer side effects. Researchers are excited about deutetrabenazine because it utilizes a deuterium modification, enhancing its stability and allowing for more consistent dosing, which can improve patient outcomes and quality of life.

What evidence suggests that deutetrabenazine might be an effective treatment for Huntington's disease?

Studies have shown that deutetrabenazine, the treatment being tested in this trial, effectively treats chorea, the involuntary movement often seen in Huntington's disease. One study found that deutetrabenazine significantly reduced these movements and improved overall motor skills in participants. More than 94% of patients with similar movement disorders, such as tardive dyskinesia, reported better movement control when taking deutetrabenazine. This suggests deutetrabenazine can help manage movement problems associated with Huntington's disease. ^{5 6 7 8 9}

Who Is on the Research Team?

Amy E Brown, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with Huntington's Disease who can walk at least 10 meters, have a certain level of chorea (involuntary movements), and are cognitively able to participate. They must not be pregnant or breastfeeding, have severe depression or speech impairments, nor any serious medical conditions that could interfere with the study.

Inclusion Criteria

I have completed at least 10th grade.

Willing and able to give written informed consent prior to performing any study procedures

My cognitive function score is 22 or higher.

Exclusion Criteria

Concurrent participation in any other investigational drug trials

I have severe difficulty speaking or cannot speak at all.

I do not have any serious or unstable health or mental conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive deutetrabenazine with dose titration to achieve optimal chorea control

Up to 10 weeks

Weekly visits for dose titration

Evaluation

Comprehensive evaluations of speech production, fine motor skills, gait, and balance using standardized assessments and 3D motion analysis

Up to 10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deutetrabenazine

Trial Overview The trial is testing Deutetrabenazine to see if it improves functional speech and walking in people with Huntington's Disease. Participants will receive this medication and their speech and gait dynamics will be monitored for changes.

How Is the Trial Designed?

Group I: Deutetrabenazine Experimental Treatment 1 Intervention

The mode of administration is oral. Subjects will be started on deutetrabenazine at a dose of 6mg/day. Dosing will be up-titrated in increments of 6mg/day per week to achieve optimal chorea control.

Deutetrabenazine is already approved in United States, China for the following indications:

Approved in United States as Austedo for:

• Chorea associated with Huntington's disease
• Tardive dyskinesia in adults

Approved in China as Austedo for:

• Chorea associated with Huntington's disease
• Tardive dyskinesia in adults

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Teva Branded Pharmaceutical Products R&D, Inc.

Industry Sponsor

Trials

258

Recruited

3,487,000+

Dr. Eric Hughes

Teva Branded Pharmaceutical Products R&D, Inc.

Chief Medical Officer since 2022

MD and PhD from Yale School of Medicine

Richard Francis

Teva Branded Pharmaceutical Products R&D, Inc.

Chief Executive Officer since 2022

Bachelor's degree in Biochemistry from the University of Manchester

Published Research Related to This Trial

In a pivotal 12-week phase III trial with 90 participants, deutetrabenazine significantly improved chorea control in Huntington's disease patients compared to placebo, demonstrating its efficacy as a treatment.

Deutetrabenazine has a similar tolerability profile to placebo, with most side effects being mild or moderate, and it may offer a better safety profile than tetrabenazine due to its favorable pharmacokinetics, allowing for lower dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deutetrabenazine: A Review in Chorea Associated with Huntington's Disease. Heo, YA., Scott, LJ.[2018]

In a study involving 36 healthy volunteers (12 extensive/intermediate metabolizers and 24 poor metabolizers), deutetrabenazine was shown to have linear pharmacokinetics and did not cause clinically significant QT interval prolongation at maximum recommended doses, indicating its safety regarding cardiac effects.

While higher doses of deutetrabenazine led to an increase in adverse events, no participants experienced cardiac-related issues, suggesting that the drug can be safely administered without significant cardiac risk in both metabolizer groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Deutetrabenazine's Potential to Delay Cardiac Repolarization Using Concentration-QTc Analysis. Schneider, F., Darpo, B., Loupe, PS., et al.[2023]

Deutetrabenazine (DTBZ) has been shown to be safe and effective for treating tardive dyskinesia and chorea in Huntington's Disease, with studies supporting its use at doses up to 72 mg daily for up to three years.

Long-term follow-up studies confirm the continued efficacy and overall safety of DTBZ, suggesting it may be a better option than traditional treatments like tetrabenazine (TBZ) in terms of safety, although direct comparisons are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of Deutetrabenazine as a Treatment Option for Chorea Associated with Huntington's Disease and Tardive Dyskinesia. Frank, S., Alakkas, A.[2023]

Deutetrabenazine, a modified version of tetrabenazine, has a longer half-life and better absorption, allowing for twice-daily dosing which can enhance patient compliance.

It effectively reduces chorea in Huntington's disease, hyperkinetic features of tardive dyskinesia, and tics in Tourette syndrome, with a lower incidence of adverse effects compared to tetrabenazine and no impact on the QT interval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deutetrabenazine: Treatment of hyperkinetic aspects of Huntington's disease, tardive dyskinesia and Tourette syndrome. Paton, DM.[2018]

Tetrabenazine was effective in reducing abnormal movements in patients, with improvements observed in 6 out of 8 patients with Huntington disease, 6 out of 10 with tardive dyskinesia, and 3 out of 8 with dystonic disorders after 3 weeks of treatment.

The medication was generally well tolerated by patients, indicating a favorable safety profile during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrabenazine and movement disorders. Asher, SW., Aminoff, MJ.[2022]

A meta-analysis of randomized controlled trials found that tetrabenazine and deutetrabenazine have similar efficacy and safety profiles in treating Huntington's disease, with no significant differences in motor scores or adverse events.

However, deutetrabenazine showed a significant advantage in reducing depression and somnolence compared to tetrabenazine, suggesting it may be a preferable option for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrabenazine Versus Deutetrabenazine for Huntington's Disease: Twins or Distant Cousins? Rodrigues, FB., Duarte, GS., Costa, J., et al.[2022]

Deutetrabenazine, an FDA-approved treatment for chorea in Huntington's disease, shows significant improvement in chorea symptoms with a favorable safety profile, having similar tolerability to placebo and primarily causing somnolence.

While its efficacy is comparable to tetrabenazine, deutetrabenazine offers a longer half-life allowing for less frequent dosing, making it a potentially more convenient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of deutetrabenazine: a novel treatment for chorea associated with Huntington's disease. Dean, M., Sung, VW.[2018]

Deutetrabenazine has a longer half-life and lower peak-to-trough fluctuations of its active metabolites compared to tetrabenazine, indicating a more stable drug exposure which could enhance its therapeutic effects.

Food intake does not significantly affect the overall exposure to deutetrabenazine's active metabolites, although it can increase the peak concentration slightly, suggesting that it can be taken with or without food without impacting its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Deutetrabenazine and Tetrabenazine: Dose Proportionality and Food Effect. Schneider, F., Stamler, D., Bradbury, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11769868/

Safety and Efficacy of Deutetrabenazine at High versus ... Deutetrabenazine is used to treat unplanned movements known as chorea, which happen in participants who have Huntington disease. At the start of ...

2. ir.tevapharm.com ir.tevapharm.com/news-and-events/press-releases/press-release-details/2025/Patients-Taking-AUSTEDO-XR-deutetrabenazine-extended-release-tablets-Reported-Symptom-Improvement-and-High-Satisfaction/default.aspx

Patients Taking AUSTEDO XR® (deutetrabenazine) extended ... Of the 209 patients with tardive dyskinesia (TD) that were surveyed, >94% reported movement improvement once treated with AUSTEDO XR® ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01795859

First Time Use of SD-809 in Huntington Disease The purpose of this study is to determine whether SD-809 tablets are effective in the treatment of chorea associated with Huntington's Disease.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5440239/

Randomized controlled trial of deutetrabenazine for tardive ... For example, deutetrabenazine significantly decreased chorea, improved overall motor function, and was well tolerated, with low rates of neuropsychiatric ...

5. austedohcp.com austedohcp.com/huntingtons-disease-chorea/3-year-study

Huntington's Disease Chorea 3-year Study Depression and Suicidality in Patients with Huntington's Disease: AUSTEDO XR and AUSTEDO can increase the risk of depression and suicidal thoughts and behavior ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11136929/

Safety of Deutetrabenazine for the Treatment of Tardive ... For chorea in Huntington disease, adverse event rates were similar for deutetrabenazine (64%) and placebo (60%). Serious adverse event rates ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/208082s000lbl.pdf

AUSTEDO (deutetrabenazine) tablets, for oral use AUSTEDO may cause parkinsonism in patients with Huntington's disease. Because rigidity can develop as part of the underlying disease process in Huntington's ...

8. austedohcp.com austedohcp.com/huntingtons-disease-chorea

Huntington's Disease (HD) Chorea IMPORTANT SAFETY INFORMATION. Depression and Suicidality in Patients with Huntington's Disease: AUSTEDO XR and AUSTEDO can increase the risk of depression ...

9. en.wikipedia.org en.wikipedia.org/wiki/Deutetrabenazine

Deutetrabenazine Deutetrabenazine, sold under the brand name Austedo, is a vesicular monoamine transporter 2 inhibitor which is used for the treatment of chorea