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

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug deutetrabenazine for Huntington's disease?

Deutetrabenazine has been shown to significantly improve chorea (involuntary movements) in patients with Huntington's disease compared to a placebo, as demonstrated in a 12-week clinical trial. It is also generally well-tolerated, with a side effect profile similar to placebo, except for some drowsiness. ^{1 2 3 4 5}

Is deutetrabenazine safe for humans?

Deutetrabenazine is generally considered safe for humans, with most side effects being mild or moderate. Long-term studies have shown it to be safe for up to three years, and it does not have a significant effect on heart rhythm at recommended doses. ^{1 2 3 6 7}

What makes the drug deutetrabenazine unique for treating Huntington's disease?

Deutetrabenazine is a modified form of tetrabenazine with a longer-lasting effect, allowing it to be taken twice daily, which can improve patient compliance. It has a lower peak concentration, potentially reducing some side effects, and unlike tetrabenazine, it does not affect the heart's QT interval. ^{1 2 3 6 8}

What is the purpose of this trial?

Examine the effects of deutetrabenazine on functional speech and gait impairment

Research Team

Amy E Brown, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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

I have severe difficulty speaking or cannot speak at all.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 (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]

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, 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]

References

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

Pharmacokinetics of Deutetrabenazine and Tetrabenazine: Dose Proportionality and Food Effect. [2022]

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

Deutetrabenazine: A Review in Chorea Associated with Huntington's Disease. [2018]

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

Tetrabenazine Versus Deutetrabenazine for Huntington's Disease: Twins or Distant Cousins? [2022]

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

Tetrabenazine and movement disorders. [2022]

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

Review of deutetrabenazine: a novel treatment for chorea associated with Huntington's disease. [2018]

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

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

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

Evaluation of Deutetrabenazine's Potential to Delay Cardiac Repolarization Using Concentration-QTc Analysis. [2023]

8. Spain pubmed.ncbi.nlm.nih.gov

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