Dystonia, PrimaryPhase 1/2AUDYTNCT04173260
An Open-label Study to Define the Safety, Tolerability and Clinical Activity of Deutetrabenazine (AUstedo) in Adult Study Subjects With DYsTonia
A Phase 1/2 study testing Deutetrabenazine 6 MG in people with Dystonia, Primary, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a single-center, open-label study of AUSTEDO in study subjects with dystonia. The study will provide preliminary experience of the safety, tolerability, and clinical activity of AUSTEDO in study subjects with dystonia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dystonia, Primary
- What is being tested?
- Deutetrabenazine 6 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Apr 2021to 31 Aug 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Study subjects with definite dystonia, as established by a movement disorder specialist.
- Study subjects of any race and either gender, age 18 or more on the date the informed consent form (ICF) is signed and with the capacity to provide voluntary informed consent.
- Study subjects able to read and understand English and the ICF and are willing to comply with all study procedures, treatment and follow-up.
- Study subjects who are taking any central nervous system acting medications (e.g., benzodiazepines, antidepressants, hypnotics), including medications for the treatment of dystonia, will be on a stable regimen for at least 30 days prior to the screening Visit, and will willing to remain on the same dose for the duration of the study.
- Female of child-bearing potential will not be pregnant and will be using an acceptable method of contraception.
- Study subjects with an MMSE >24.
Who cannot join
- Exposure to dopamine blockers prior to the onset of dystonia that could, in the investigator's opinion, have caused dystonia.
- Study subjects with genetically-confirmed dopa-responsive dystonia.
- Study subjects with a diagnosis of Parkinson's or an atypical parkinsonian syndrome.
- Study subjects with a history of bipolar disorder or major depression, or the presence of active depression.
- Study subjects with a history of a suicide attempt or suicidal ideations, as well as the presence of active suicidal ideation as detailed on the C-SSRS administered during Visit 1.
- Study subjects with a history of schizophrenia or schizophrenia spectrum disorders.
Show all 15Show fewer
- Treatment with tetrabenazine, reserpine, valbenazine, a monoamino oxidase inhibitor, a-methyl-p-tyrosine, strong anticholinergic medications, metoclopramide, antipsychotics, dopamine agonists, levodopa, and/or stimulants within 30 days of screening.
- Treatment with botulinum toxin less than 11 weeks prior to screening (Visit 1); subjects receiving injections sooner than every 12 weeks will be excluded if their next injection is scheduled farther than 6 days from screening.
- Presence of a neurologic condition that could confound dystonia assessments.
- Study subjects with a history of clinically relevant hepatic disease.
- Study subjects with a history of renal insufficiency.
- Any unstable medical illness.
- A corrected QT (Bazett) interval of 450 (458) milliseconds in men or 460 (472) milliseconds in women on 12-lead ECG at screening, or a history of cardiac arrhythmias.
- Study subjects participating in any drug or device clinical investigation concurrently or within 30 days prior to screening for this study.
- Study subjects with a known hypersensitivity or contraindication to the study drug or its components.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19107
About this study
Official title: The AUDYT Trial: An Open-label Study to Define the Safety, Tolerability and Clinical Activity of Deutetrabenazine (AUstedo) in Adult Study Subjects With DYsTonia
This is a single-center, open-label study of AUSTEDO in study subjects with dystonia. The study will provide preliminary experience of the safety, tolerability, and clinical activity of AUSTEDO in study subjects with dystonia. Study duration will be up to 13 weeks from screening (Visit 1) to the post treatment evaluation (Visit 5). Treatment period from drug initiation to final on-treatment Visit will be 12 weeks, or less, as follows: during the ramp-up period, study drug will start at 12 mg/day (6 mg twice daily) and will be titrated weekly by 6 mg/day increments until either 1) the maximal allowable dose (48 mg/day) is reached, or 2) dose-limiting side-effects occur. In study subjects receiving a strong CYP2D6 inhibitor, the maximum allowed dose of AUSTEDO will be 36 mg/day, reducing study duration (due to a reduction in the ramp-up period) to 11 weeks. Study subjects who experience dose-limiting side effects will be maintained on their maximum tolerated dose. Once the maximal dose is established for each participant, they will complete 6 continuous weeks on this dose (maintenance period), followed by a 1-week washout. For study subjects unable to titrate up to 48 mg/day due to side effects, the 6 weeks of maintenance will start once they reduce the study drug back to the maximum well-tolerated dose. Adverse events will be monitored throughout the study and will be reported after drug initiation. Dose reductions, suspensions, and withdrawals due to adverse events will be recorded. ECG readings will be measured at screening, during week 2, during the first week of the maintenance period (whenever this is established to be, typically week 7 for subjects able to titrate up to 48 mg/day), immediately before washout (week 12 for those study subjects who are able to titrate up to 48 mg/day) and during week 13. Assessment of Columbia Suicide Severity Rating Scale and Epworth Sleepiness Scale scores will occur at screening and all clinic Visits. The Mini Mental (MMSE) Scale will be performed at screening and at the final on-treatment Visit (week 12). A video examination of the study subjects will be made at screening (right before initiation of the study drug), and after 6 weeks on AUSTEDO at a steady dose (right before drug cessation). Part III of the MDS-UPDRS will be performed at both of these Visits as well to screen for the appearance of drug-induced parkinsonism. Videos will be sent to raters blinded to treatment, Visit number and recording date.
- Conditions
- Dystonia, Primary
- Being tested
- Deutetrabenazine 6 MG
- Medical subject headings
- Dystonic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deutetrabenazine 6 MGDrug
Increasing doses of Deutetrabenazine
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm - Oral Deutetrabenazine | Experimental | This is the only arm for this trial. All subjects will receive oral Deutetrabanazine. Receives: Drug: Deutetrabenazine 6 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Study Subjects Able to Titrate up to the Maximum Tolerated Dose
Proportion of study subjects able to titrate up to 48 mg/d (or up to 36 mg/d if receiving a strong CYP2D6 inhibitor) and able to complete the study at this dosage
Measured: 3 months
Secondary outcomes (6)
Number of Participants With Change in Suicidality
Documentation of change in the Columbia Suicide Severity Rating Scale. Items on this scale are both binary (Yes/No) and numeric (0-5). "No" answers and lower numeric values indicate a better outcome.
Measured: Baseline and 3 months
Change in Median Daytime Somnolence Score Among Subjects
Documentation of change in the Stanford Sleepiness Scale. Scale was assessed at the initial and last study visit; difference was calculated between both scores, and reported herein as a median among all participants' scores and full range.
Items on this scale are numeric (1-7). Lower numeric values indicate a better outcome.
Measured: Baseline and 3 months
Change in Median MMSE Score Among Subjects
Documentation of change in the Mini Mental Scale. Scale was assessed at the initial and last study visit; difference was calculated between both scores, and reported herein as a median among all participants' scores and full range.
The higher the total score on this scale, the better the outcome. Values range from 0 to a maximum of 30.
Measured: Baseline and 3 months
Development of Parkinsonism, as Determined by Change in Median MDS-UPDRS III Score Among Subjects
Documentation of change in the MDS-Unified Parkinson's Disease Rating Scale, Part III. Scale was assessed at the initial and last study visit; difference was calculated between both scores, and reported herein as a median among all participants' scores and full range.
The lower the total score on this scale, the better the outcome. Values range from 0 to a maximum of 128.
Measured: Baseline and 3 months
Change in Median PGI-I Score
Documentation of change in the Patient Global Impression of Improvement Scale (PGI-I). This is a Likert scale, with values from 1-7. A value of 1 indicates the best outcome. A value of 4 indicates no perceived change.
Measured: Baseline and 3 months
Change in Dystonia Severity, as Determined by the Change in Median GDS Score
Documentation of change in the Global Dystonia Rating Scale. Scale was assessed blindly from videos captured at the initial and last study visit; difference was calculated between both scores, and reported herein as a median among all participants' scores and full range.
The lower the total score on this scale, the better the outcome. Values range from 0 to a maximum of 140.
Measured: Baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2019
- Study start29 Apr 2021
- Primary completion15 Mar 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Dystonia, PrimaryStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04173260
- Sponsor's protocol ID
- 10070487
- Acronym
- AUDYT
- Status last verified
- Sep 2024
- First submitted
- 18 Nov 2019
- Last updated
- 20 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The AUDYT Trial: An Open-label Study to Define the Safety, Tolerability and Clinical Activity of Deutetrabenazine (AUstedo) in Adult Study Subjects With DYsTonia
- ClinicalTrials.gov ID
- NCT04173260
- Acronym / sponsor ID
- AUDYT / 10070487
- Conditions
- Dystonia, Primary
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc.
- Study start
- 29 Apr 2021 (actual)
- Primary completion
- 15 Mar 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 21 Nov 2019 (actual)
- Results
- Posted 12 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-center, open-label study of AUSTEDO in study subjects with dystonia. The study will provide preliminary experience of the safety, tolerability, and clinical activity of AUSTEDO in study subjects with dystonia. Study duration will be up to 13 weeks from screening (Visit 1) to the post treatment evaluation (Visit 5). Treatment period from drug initiation to final on-treatment Visit will be 12 weeks, or less, as follows: during the ramp-up period, study drug will start at 12 mg/day (6 mg twice daily) and will be titrated weekly by 6 mg/day increments until either 1) the maximal allowable dose (48 mg/day) is reached, or 2) dose-limiting side-effects occur. In study subjects receiving a strong CYP2D6 inhibitor, the maximum allowed dose of AUSTEDO will be 36 mg/day, reducing study duration (due to a reduction in the ramp-up period) to 11 weeks. Study subjects who experience dose-limiting side effects will be maintained on their maximum tolerated dose. Once the maximal dose is established for each participant, they will complete 6 continuous weeks on this dose (maintenance period), followed by a 1-week washout. For study subjects unable to titrate up to 48 mg/day due to side effects, the 6 weeks of maintenance will start once they reduce the study drug back to the maximum well-tolerated dose. Adverse events will be monitored throughout the study and will be reported after drug initiation. Dose reductions, suspensions, and withdrawals due to adverse events will be recorded. ECG readings will be measured at screening, during week 2, during the first week of the maintenance period (whenever this is established to be, typically week 7 for subjects able to titrate up to 48 mg/day), immediately before washout (week 12 for those study subjects who are able to titrate up to 48 mg/day) and during week 13. Assessment of Columbia Suicide Severity Rating Scale and Epworth Sleepiness Scale scores will occur at screening and all clinic Visits. The Mini Mental (MMSE) Scale will be performed at screening and at the final on-treatment Visit (week 12). A video examination of the study subjects will be made at screening (right before initiation of the study drug), and after 6 weeks on AUSTEDO at a steady dose (right before drug cessation). Part III of the MDS-UPDRS will be performed at both of these Visits as well to screen for the appearance of drug-induced parkinsonism. Videos will be sent to raters blinded to treatment, Visit number and recording date.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention arm - Oral Deutetrabenazine | Experimental | Drug: Deutetrabenazine 6 MGThis is the only arm for this trial. All subjects will receive oral Deutetrabanazine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Study subjects with definite dystonia, as established by a movement disorder specialist.
- Study subjects of any race and either gender, age 18 or more on the date the informed consent form (ICF) is signed and with the capacity to provide voluntary informed consent.
- Study subjects able to read and understand English and the ICF and are willing to comply with all study procedures, treatment and follow-up.
- Study subjects who are taking any central nervous system acting medications (e.g., benzodiazepines, antidepressants, hypnotics), including medications for the treatment of dystonia, will be on a stable regimen for at least 30 days prior to the screening Visit, and will willing to remain on the same dose for the duration of the study.
- Female of child-bearing potential will not be pregnant and will be using an acceptable method of contraception.
Key exclusion criteria (15 listed)
- Exposure to dopamine blockers prior to the onset of dystonia that could, in the investigator's opinion, have caused dystonia.
- Study subjects with genetically-confirmed dopa-responsive dystonia.
- Study subjects with a diagnosis of Parkinson's or an atypical parkinsonian syndrome.
- Study subjects with a history of bipolar disorder or major depression, or the presence of active depression.
- Study subjects with a history of a suicide attempt or suicidal ideations, as well as the presence of active suicidal ideation as detailed on the C-SSRS administered during Visit 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deutetrabenazine 6 MGIncreasing doses of Deutetrabenazine | Drug | Intervention arm - Oral Deutetrabenazine |
Primary outcome
Proportion of Study Subjects Able to Titrate up to the Maximum Tolerated Dose
Time frame: 3 months
Proportion of study subjects able to titrate up to 48 mg/d (or up to 36 mg/d if receiving a strong CYP2D6 inhibitor) and able to complete the study at this dosage
6 secondary outcomes
Number of Participants With Change in Suicidality
Time frame: Baseline and 3 months
Change in Median Daytime Somnolence Score Among Subjects
Time frame: Baseline and 3 months
Change in Median MMSE Score Among Subjects
Time frame: Baseline and 3 months
Development of Parkinsonism, as Determined by Change in Median MDS-UPDRS III Score Among Subjects
Time frame: Baseline and 3 months
Change in Median PGI-I Score
Time frame: Baseline and 3 months
Change in Dystonia Severity, as Determined by the Change in Median GDS Score
Time frame: Baseline and 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Deutetrabenazine 6 MG in people with Dystonia, Primary, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Study Subjects Able to Titrate up to the Maximum Tolerated Dose (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2024.