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Record W4306292918 · doi:10.1007/s40263-022-00956-8

The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open-Label Extension Study

2022· article· en· W4306292918 on OpenAlexaff
Samuel Frank, Claudia Testa, Mary Edmondson, Jody Goldstein, Elise Kayson, Blair R. Leavitt, David Oakes, Christine J. O’Neill, Christina Vaughan, Jacquelyn Whaley, Nicholas J. Gross, Mark Forrest Gordon, Juha‐Matti Savola, David Stamler, Margaret Bockus, Stephanie Leyva, Victoria Snively, Cynthia Wong, William Mallonee, Gregory Suter, Joseph Jankovic, Joohi Jimenez‐Shahed, Christine Hunter, Daniel O. Claassen, Lauren West, O Román, Victor Sung, Jenna Smith, Ronda Clouse, Marie Saint‐Hilaire, Denyse Turpin, Raymond James, Ramon L. Rodriguez, Kyle Rizer, Karen E. Anderson, Hope Heller, Alexis Ahmad, Susan R. Criswell, Brad A. Racette, Frederick C. Nucifora, Gregory Churchill, MaryJane Ong, Tilak Mendis, Neila Mendis, Carlos Singer, Jane S. Paulsen, Jane Kerr, Richard Dubinsky, Carolyn Steele Gray, Stewart A. Factor, Elaine Sperin, Eric Molho, Sharon Evans, Breanna Nickels, Courtney Bergen, Jessica Jaynes, Christina Reeves, Vicki Segro, Ali Samii, Emily Christopher, Debra del Castillo, Sylvain Chouinard, Peggy Perry-Trice, Sherali Esmail, Wai Lun Alan Fung, Clare Gibbons, Amy Colcher, Cory Hackmyer, Andrew McGarry, Kevin J. Klos, Mark Gudesblatt, Daniel Schneider, Rohit Dhall, Edith Simpson, Joanne Wojcieszek, Andrea Hurt, Kathrin LaFaver, Annette Robinson, Fredy J. Revilla, Andrew P. Duker, Erin Neefus, Hilary Wilson, David Shprecher, Tyler Hohnholt, Paola Wall, James T. Boyd, Emily Houston, Eric S. Farbman, Shamine Poynor, Pinky Agarwal, Julissa Leon, Shirley Eberly, Arthur Watts, Pierre N. Tariot, Andrew Feigin, Scott Evans, Christopher A. Beck

Bibliographic record

VenueCNS Drugs · 2022
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsUniversity of British Columbia
FundersTeva Pharmaceutical Industries
KeywordsMedicineChoreaTolerabilityAdverse effectSomnolenceHuntington's diseaseAkathisiaPediatricsInternal medicineAnesthesiaDiseasePsychiatry

Abstract

fetched live from OpenAlex

BACKGROUND: Deutetrabenazine is approved in the USA, China, Australia, Israel, Brazil, and South Korea for the treatment of chorea associated with Huntington disease. OBJECTIVE: We aimed to evaluate the long-term safety and tolerability of deutetrabenazine for the treatment of Huntington disease. METHODS: This open-label, single-arm, multi-center study included patients who completed a double-blind study (Rollover) and patients who converted overnight from a stable tetrabenazine dose (Switch). Exposure-adjusted incidence rates (adverse events per person-year) were calculated. Efficacy was analyzed using a stable post-titration timepoint (8 weeks). Changes in the Unified Huntington's Disease Rating Scale total motor score and total maximal chorea score from baseline to week 8, as well as those from week 8 to week 145 (or the last visit on the study drug if that occurred earlier), were evaluated as both efficacy and safety endpoints during the study. RESULTS: Of 119 patients (Rollover, n = 82; Switch, n = 37), 100 (84%) completed ≥ 1 year of treatment. End-of-study exposure-adjusted incidence rates for adverse events in Rollover and Switch, respectively, were: any, 2.57 and 4.02; serious, 0.11 and 0.14; leading to dose suspension, 0.05 and 0.04. Common adverse events (≥ 4% either cohort) included somnolence (Rollover, 20%; Switch, 30%), depression (32%; 22%), anxiety (27%; 35%), insomnia (23%; 16%), and akathisia (6%; 11%). Adverse events of interest included suicidality (9%; 5%) and parkinsonism (4%; 8%). Mean dose at week 8 was 38.1 mg (Rollover) and 36.5 mg (Switch). Mean dose across cohorts after titration was 37.6 mg; at the final visit, mean dose across cohorts was 45.7 mg. Patients showed minimal change in the Unified Huntington's Disease Rating Scale total maximal chorea scores with stable dosing from weeks 8-145 or at the end of treatment, but total motor score increased versus week 8 (mean change [standard deviation]: 8.2 [11.9]). There were no unexpected adverse events upon drug withdrawal, and mean (standard deviation) total maximal chorea scores increased 4.7 (4.6) units from week 8 to 1-week follow-up. CONCLUSIONS: Adverse events observed with long-term deutetrabenazine exposure were consistent with previous studies. Reductions in chorea persisted over time. Upon treatment cessation, there was no unexpected worsening of chorea. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01897896.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.059
GPT teacher head0.336
Teacher spread0.277 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations31
Published2022
Admission routes1
Has abstractyes

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