Research

JAMA Neurology | Original Investigation

Safety of Converting From Tetrabenazine

to Deutetrabenazine for the Treatment of Chorea
Samuel Frank, MD; David Stamler, MD; Elise Kayson, MS, RNC, ANP; Daniel O. Claassen, MD; Amy Colcher, MD;
Charles Davis, PhD; Andrew Duker, MD; Shirley Eberly, MS; Lawrence Elmer, MD, PhD; Erin Furr-Stimming, MD;
Mark Gudesblatt, MD; Christine Hunter, RN; Joseph Jankovic, MD; Sandra K. Kostyk, MD, PhD; Rajeev Kumar, MD;
Clement Loy, MBBS, FRACP, PhD; William Mallonee, MD; David Oakes, PhD; Burton L. Scott, MD, PhD;
Victor Sung, MD; Jody Goldstein, BS; Christina Vaughan, MD; Claudia M. Testa, MD, PhD; for the Huntington Study
Group/Alternatives for Reducing Chorea in Huntington Disease Investigators

Supplemental content
IMPORTANCE Tetrabenazine is efficacious for chorea control; however, tolerability concerns
exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a
double-blind, placebo-controlled study.

OBJECTIVES To evaluate the safety and explore the efficacy of conversion from tetrabenazine
to deutetrabenazine in patients with chorea associated with Huntington disease (HD).

DESIGN, SETTING, AND PARTICIPANTS In this ongoing, open-label, single-arm study that
started on December 21, 2013, 37 patients at 13 Huntington Study Group sites in the United
States and Australia who were taking stable doses of tetrabenazine that provided a
therapeutic benefit were switched overnight to deutetrabenazine therapy. After week 1, the
deutetrabenazine dose was titrated on a weekly basis for optimal chorea control.

INTERVENTIONS Deutetrabenazine administration at a dosage thought to provide

comparable systemic exposure to the active metabolites of the prior, stable tetrabenazine
regimen.

MAIN OUTCOMES AND MEASURES Safety measures included adverse events (AEs), clinical
laboratory tests, vital signs, electrocardiograms, and validated scales. Changes in the Unified
Huntington’s Disease Rating Scale total maximal chorea score and total motor score were
efficacy end points.

RESULTS Of the 53 patients with HD screened for the study, 37 ambulatory patients with
manifest HD (mean [SD] age, 52.4 [11.5] years; 22 [59%] male and 15 [41%] female; 36 white
[97.3%]) were enrolled. Deutetrabenazine was generally well tolerated, with low rates of
neuropsychiatric AEs. Safety scales did not reveal subclinical toxicity with deutetrabenazine
treatment. Rates of dose reduction or suspension attributable to AEs were also low. Chorea
control, as measured by the total maximal chorea score, was maintained at week 1 and
significantly improved at week 8 (mean [SD] change from baseline, 2.1 [3.2]; P < .001).

CONCLUSIONS AND RELEVANCE In patients with chorea, overnight conversion to

deutetrabenazine therapy provided a favorable safety profile and effectively maintained
chorea control.

Author Affiliations: Author

affiliations are listed at the end of this
article.
Group Information: The Huntington
Study Group/Alternatives for
Reducing Chorea in Huntington
Disease Investigators are listed at the
end of this article.
Corresponding Author: Samuel
Frank, MD, Harvard Medical School,
330 Brookline Ave, Kirstein Bldg,
JAMA Neurol. doi:10.1001/jamaneurol.2017.1352 Room 228, Boston, MA 02215
Published online July 10, 2017. (sfrank2@bidmc.harvard.edu).

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 Research Original Investigation
H
untington disease (HD) is a hereditary, progressive,
neurodegenerative disorder characterized by chorea
and other motor symptoms, cognitive dysfunction,
and psychiatric symptoms. Up to 90% of patients with HD have
chorea that can interfere with daily function and may cause
injury.1,2 Tetrabenazine was the first drug approved by the US
Food and Drug Administration for chorea associated with HD.3
High peak plasma concentrations and large plasma fluctua-
tions may contribute to the tolerability issues observed in some
patients with tetrabenazine use.4 Deutetrabenazine, a novel
molecule that contains 6 deuterium atoms in place of 6 hy-
drogen atoms in specific positions in the tetrabenazine mol-
ecule, was approved for treating chorea associated with HD in
2017.5 Clinical evaluation in the First-HD trial found that deu-
tetrabenazine provides significant chorea and motor improve-
ment while maintaining a favorable safety profile when com-
pared with placebo.6 The efficacy and excellent safety profile
were attributed to the unique pharmacokinetic profile of deu-
tetrabenazine, which enables comparable systemic exposure
at lower doses, lower peak concentrations, and reduced plasma
fluctuations.5 The current open-label study evaluated the
safety and explored the efficacy of an overnight conversion
from tetrabenazine to deutetrabenazine therapy with subse-
quent optional dose adjustment in patients with HD receiv-
ing a stable tetrabenazine regimen for chorea.
Methods
Study Design
This is an ongoing, open-label, single-arm study that started
on December 21, 2013, at 13 Huntington Study Group sites in
the United States and Australia. In-person study visits were
conducted at baseline (day 0), on the last day of tetrabena-
zine use, and at weeks 1, 4, and 8 after overnight conversion
to deutetrabenazine therapy. Telephone consultations were
made at weeks 2, 3, and 7. Written approvals from an inde-
pendent ethics committee or institutional review board were
received before the initiation of this study. Western Institu-
tional Review Board was used at all sites except for the
following individual institutional review boards: Western Syd-
ney Local Health District Human Research Ethics Commit-
tee, University of Alabama Birmingham, Duke University
Health System, The Cooper Health System, Vanderbilt Uni-
versity Medical Center, and Rocky Mountain Movement Dis-
orders Center. Institutional review board approval was also ob-
tained at the Chesapeake Insitutional Review Board and
centrally at the Research Subjects Review Board at the Uni-
versity of Rochester. An independent, qualified health care pro-
fessional evaluated all patients to determine patient capacity
to consent to participate. If patients lacked the capacity to
provide informed consent, a legally authorized representa-
tive provided written informed consent, in addition to the
patients’ provided written assent.
Patients
Patients were eligible if they were ambulatory adults with mani-
fest HD indicated by characteristic motor examination fea-
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Tetrabenazine to Deutetrabenazine Conversion for Chorea Treatment
Key Points
Question Is overnight treatment conversion from tetrabenazine
to deutetrabenazine safe in patients with Huntington disease?
Findings In this open-label, single-arm study, 37 patients with
chorea associated with Huntington disease switched overnight
from a stable, therapeutic tetrabenazine regimen to
deutetrabenazine. Deutetrabenazine was generally safe and well
tolerated, with chorea scores maintained at the end of week 1 of
deutetrabenazine therapy and improved at week 8.
Meaning Chorea control may be safely maintained after an
overnight switch from tetrabenazine to deutetrabenzine.
tures and an expanded CAG repeat sequence (≥37) and were
receiving a stable tetrabenazine regimen for 8 weeks or lon-
ger that provided a therapeutic benefit for chorea control. Pa-
tients had a total functional capacity score of 5 or higher at
screening. The total functional capacity score is a 13-point stan-
dardized disease staging scale that assesses an individual’s abil-
ity to perform tasks in 5 functional areas: to perform chores,
perform activities of daily living, work, manage finances, and
live at home. Higher scores indicate earlier disease and better
functional status. In early HD, the mean (SD) decline is 0.63
(0.75) points per year.7 Enrolled patients were required to have
daily access to reliable caregiver support to oversee study drug
administration, ensure attendance at study visits, and pro-
vide another level of oversight for safety. Patients with more
severe functional impairment as indicated by a total func-
tional capacity score of 5 to 7 at screening were required to have
a live-in caregiver.
Patients with serious undertreated psychiatric illness were
excluded; however, concomitant stable antidepressant therapy
was permitted during the study. Patients with active or past
suicidal ideation, thoughts, or behavior were excluded. Pa-
tients were excluded if they scored 11 or higher on the Hospi-
tal Anxiety and Depression Scale, 11 or higher on the Swallow-
ing Disturbance Questionnaire, or 3 or higher on the dysarthria
score of the Unified Parkinson’s Disease Rating Scale. Con-
comitant use of dopamine receptor antagonists, dopamine ago-
nists, levodopa, reserpine, N-methyl-D-aspartate receptor an-
tagonists, or monoamine oxidase inhibitors within 30 days of
screening was also exclusionary.
Dosing
Patients were required to have been receiving a stable tetra-
benazine regimen (≥8 weeks) to be eligible. Each patient’s in-
dividualized tetrabenazine treatment regimen was deter-
mined by his or her primary health care professional
independently of this study and before study participation.
Masked CYP2D6 (OMIM 124030) genotyping was conducted
at screening and remained masked throughout the study.
Therefore, subsequent dosing decisions were made without
knowledge of the participants CYP2D6 metabolism status. The
initial deutetrabenazine daily dose was approximately half
the prior tetrabenazine daily dose determined to profile
comparable systemic exposure (area under the curve) to ac-
tive metabolites (eTable in the Supplement). One week after
jamaneurology.com
 Tetrabenazine to Deutetrabenazine Conversion for Chorea Treatment
overnight conversion to deutetrabenazine, the investigator, in
consultation with the patient and caregiver, could begin weekly
dose adjustments of deutetrabenazine, if needed, to achieve
optimal chorea control. Dose adjustments were made on the
basis of assessment of tolerability and chorea control by the
investigator. The maximum total daily dose of deutetrabena-
zine that could be used was 72 mg; however, if the patient was
receiving a strong CYP2D6 inhibitor (eg, bupropion, parox-
etine, fluoxetine), the maximum total daily dose permitted was
42 mg.
Assessments
Safety measures included assessment of adverse events
(AEs), clinical laboratory tests, physical and neurologic
examinations, vital signs, electrocardiograms, and the fol-
lowing scales: Unified Huntington’s Disease Rating Scale
(UHDRS),8 Hospital Anxiety and Depression Scale,9 Colum-
bia Suicide Severity Rating Scale,10 Barnes Akathisia Rating
Scale,11 Swallowing Disturbance Questionnaire,12 Unified
Parkinson’s Disease Rating Scale dysarthria item,13 Montreal
Cognitive Assessment,14 and Epworth Sleepiness Scale.15
The changes from baseline in the UHDRS total maximal
chorea (TMC) score and total motor score (TMS) were evalu-
ated as exploratory efficacy end points. The TMC score is a sub-
set of the TMS; for the TMC and TMS, higher scores indicate
greater motor signs.
Safety
Adverse events were tabulated, and treatment-emergent
AEs were defined as events that began after initiation of
study drug treatment that were not present at baseline
or, if present at baseline, that worsened in severity. Two-
sided paired t tests were used for descriptive analysis of
changes from baseline for the Epworth Sleepiness Scale,
Swallowing Disturbance Questionnaire, Unified Parkinson’s
Disease Rating Scale dysarthria, and Barnes Akathisia Rating
Scale.
Efficacy
Descriptive statistics were conducted for the UHDRS TMC score
and TMS for the actual data presented by visit and changes from
baseline. Two-sided paired t tests were performed to analyze
changes from baseline. Baseline values used for calculating
change from baseline for TMC score and TMS were the mean
of the values from the screening and day 0 baseline visits.
Lower scores on the TMC and TMS indicate less severe impair-
ment. Participants were receiving a stable tetrabenazine
regimen for at least 8 weeks before the screening visit and con-
tinued this regimen through the day 0 baseline visit before the
day 1 change to deutetrabenazine.
Statistical Analysis
Because this was an open-label safety study, statistical con-
siderations did not determine sample size. All analyses in-
clude observed data, with no imputation of missing values.
P < .05 (2-sided) was considered statistically significant. Sta-
tistical analyses were performed using SAS statistical soft-
ware (SAS Institute Inc).
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Original Investigation Research
Figure 1. Flow of Study Patients
53 Assessed for eligibility
16 Excluded
6 Used exclusionary medication
4 Did not meet other inclusion criteria
6 Other
37 Enrolled
1 Withdrew (investigator decision)
36 Converted to deutetrabenazine,
ongoing participation
36 Included in efficacy analysis
37 Included in safety analysis
After screening for eligibility, a total of 37 patients were enrolled. Of the 37
patients, 1 patient withdrew and all others continued in the ongoing study.
Results
Baseline Characteristics
A total of 53 patients were assessed for eligibility in the study.
Of these, 14 patients were excluded (6 were taking exclusion-
ary medications, 4 did not meet inclusion criteria, 2 had se-
vere suicidal ideation or depression, 1 had abnormal labora-
tory values, and 1 was excluded for other reasons) and 2 patients
declined to participate in the study. Thus, 37 ambulatory pa-
tients with manifest HD (mean [SD] age, 52.4 [11.5] years; 22
[59%] male and 15 [41%] female; 36 white [97.3%]) were en-
rolled (Figure 1). Table 1 lists baseline characteristics, includ-
ing the baseline TMC scores and TMSs. A total of 26 patients
(70%) were being treated with antidepressants at baseline.
Dosage
The initial median deutetrabenazine daily dose was 18.0 mg,
approximately half the prior median tetrabenazine daily dose
(37.5 mg). After dose adjustment, the median deutetrabena-
zine daily doses were 30.0 mg at week 4 (n = 37) and 36.0 mg
at week 8 (n = 35). Eighteen of 37 participants (49%) were tak-
ing the same dose at the week 8 visit as they were taking or
assigned at week 4.
Safety Outcomes
A total of 20 patients (54%) reported at least 1 treatment-
emergent adverse event (Table 2). No AEs of worsening of cho-
rea were reported in this study. Adverse events leading to dose
reduction (4 [11%]) or dose suspension (1 [3%]) were ob-
served, and no patient withdrew because of an AE. There were
no clinically significant differences in laboratory values, vital
signs, body weight, or electrocardiogram findings between
baseline and week 8. Two patients (5%) experienced mild de-
pression; the association with deutetrabenazine was rated as
possible by the site investigators. There were 9 reported cases
of somnolence, of which 6 (67%) were mild; among the re-
maining 3, 1 case required dose reduction and 1 required dose
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 Research Original Investigation Tetrabenazine to Deutetrabenazine Conversion for Chorea Treatment

Table 1. Baseline Characteristics of the Study Patientsa Table 2. TEAEs Occurring in at Least 4% of Patients
Finding No. (%) of Patients
Characteristic (N = 37) TEAE (N = 37)
Patient demographic characteristics Any 20 (54)
Age, y 52.4 (11.5) Somnolence 9 (24)
Female, No. (%) 15 (41) Fall 4 (11)
White, No. (%) 36 (97) Nasopharyngitis 3 (8)
Patient clinical characteristics Anxiety 2 (5)
CAG repeat length 44.5 (3.3) Diarrhea 2 (5)
Body mass indexb 23.9 (4.7) Constipation 2 (5)
Weight, kg 71.4 (16.6) Dry mouth 2 (5)
UHDRS total functional capacity 8.3 (2.1) Depression 2 (5)
UHDRS total maximal chorea 12.5 (5.2) Irritability 2 (5)
UHDRS total motor score 38.5 (18.7) Abbreviation: TEAE, treatment-emergent adverse event.
Abbreviation: UHDRS, Unified Huntington’s Disease Rating Scale.
a
Data are presented as mean (SD) unless otherwise indicated.
b
Calculated as weight in kilograms divided by height in meters squared. Figure 2. Mean Change in Total Maximal Chorea (TMC) Score

Mean Change in TMC Score From Baseline

suspension. One patient (3%) experienced a serious AE of de- 2
hydration, possibly related to the study drug; the patient con-
tinued in the study without change in dose, and dehydration 1

resolved. There were no deaths reported in this study. Dys- 0

phagia was not reported as an AE, and Swallowing Distur-
bance Questionnaire scores did not change significantly dur- –1 a

ing the study.

–2

Deutetrabenazine Deutetrabenazine Deutetrabenazine

Efficacy Outcomes –3
(18.0 mg) (30.0 mg) (36.0 mg)
The mean (SD) TMS at baseline was 37.7 (18.6), and the mean (n = 37) (n = 37) (n = 36)
–4
(SD) TMC score was 12.5 (5.2). The mean (SD) reduction in TMC 0 1 2 3 4 5 6 7 8 9
score from baseline to week 1 was 0.7 (2.6) UHDRS units Length of Deutetrabenazine Treatment, wk

(P = .10) (Figure 2). The mean (SD) reduction in TMS from base-
line was 2.1 (5.4) UHDRS units (P = .02) at week 1 after dose con-
version (Figure 3). The mean (SD) reduction in TMC score from
baseline to week 4 was 0.6 (3.0) units (P = .21) (Figure 2). Cho-
rea control improved compared with baseline at week 8 (2.1
[3.2]; P < .001). The mean (SD) TMS was unchanged com-
pared with baseline at week 4 (1.7 [8.3]; P = .22) and week 8
(2.4 [8.7]; P = .10).
Discussion
Overnight treatment conversion from tetrabenazine 3 times
daily to deutetrabenazine twice daily can safely maintain cho-
rea control in patients with HD. Deutetrabenazine therapy was
generally well tolerated by patients after the overnight con-
version from tetrabenazine. Adherence with a twice-daily
medication was excellent and may be attributable to simpli-
fied medication regimens compared with existing therapies.
The favorable safety profile observed in this study is reflec-
tive of the findings in the First-HD study, which supports the
hypothesis that deuterium substitution–mediated attenua-
tion of drug metabolism allows for maximal efficacy through
dose adjustment while maintaining tolerability in patients with
HD.6 The safety of deutetrabenazine is further highlighted by
the low rates of depression and anxiety observed in partici-
The TMC score was assessed during 8 weeks. The TMC assessments at baseline
(blue dotted line) and weeks 1, 4, and 8 are represented for the median daily
doses of deutetrabenazine. Error bars represent SEM.
a
P < .001.
pants up to week 8 after dose conversion. Although patients
with active or undertreated psychiatric symptoms, such as de-
pression, were excluded according to the study design, pa-
tients receiving stable antidepressant treatment were en-
rolled. There was a notable absence of suicidal ideation and
parkinsonism during this 8-week study. Because this cohort
is a part of an ongoing, long-term safety study, the safety pro-
file of those patients with impaired CYP2D6 metabolism has
not been included in this early safety analysis because CYP2D6
genetic variant status remains masked to investigators and par-
ticipants. In addition, the results of this open-label study should
be interpreted with caution because this study was not ran-
domized or masked.
Limitations
This study was performed with an open-label design without
a control group by unmasked site investigators determining
chorea and TMSs in unmasked patients who had treatment con-
verted from tetrabenazine to deutetrabenazine, factors that
may impart treatment bias. Therefore, all efficacy findings re-
ported in this study should be considered to be exploratory.

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 Tetrabenazine to Deutetrabenazine Conversion for Chorea Treatment Original Investigation Research

patients thought that the combination of chorea level, effect

Figure 3. Mean Change in Total Motor Score (TMS) After Switch
of chorea on the specific patient, and drug tolerance justified
3 further dose adjustments, up or down, to maximize overall pa-
tient status. The TMC score improved at week 8 compared with
2
Mean Change in TMS From Baseline

baseline, suggesting that patients need to be reassessed for tol-

Deutetrabenazine Deutetrabenazine Deutetrabenazine erability and chorea control after initial treatment conversion
1
(18.0 mg) (30.0 mg) (36.0 mg)
(n = 37) (n = 37) (n = 36) and any subsequent dose adjustments. The improvement in
0
chorea raises the possibility that some patients were not able
–1 a to tolerate higher doses of tetrabenazine or, despite being
stable, may have had an incomplete response on tetrabena-
–2
zine. Patients in either circumstance may be more likely to en-
–3 roll in this type of study compared with other patients receiv-
ing a stable tetrabenazine regimen, creating an ascertainment
–4 bias. The starting dose for conversion may also have been too
0 1 2 3 4 5 6 7 8 9
Length of Deutetrabenazine Treatment, wk low in some patients.

The TMS was evaluated during 8 weeks. The TMS assessments at baseline (blue
dotted line) and weeks 1, 4, and 8 are represented for the median daily doses of
deutetrabenazine. Error bars represent SEM.
Conclusions
a
P = .02. The patients enrolled in this study were experiencing chorea
and receiving tetrabenazine with clinical benefit before treat-
Because the deutetrabenazine starting dose was thought to ment conversion. This proof-of-concept study reveals that
match the systemic active metabolite exposure achieved with chorea control can be safely maintained when converting
the prior tetrabenazine dose, baseline levels of chorea were ex- from tetrabenazine to deutetrabenazine, with a favorable
pected to be maintained but not necessarily improve after the safety profile. Change from a nondeuterated to a deuterium
switch to deutetrabenazine therapy. Worsening of chorea was substituted compound can achieve treatment goals with
not observed. With optional continued dose adjustments dur- fewer doses given across the day, lower total daily dose, and
ing 8 weeks, chorea control improved. There are a few expla- equivalent or potentially improved tolerance, all important
nations for continued dose adjustment after 4 weeks in half considerations in populations with neurodegenerative
of the patients. Doses could be adjusted if site investigators and disease.

ARTICLE INFORMATION
Accepted for Publication: May 10, 2017.
Published Online: July 10, 2017.
doi:10.1001/jamaneurol.2017.1352
Author Affiliations: Department of Neurology,
Harvard Medical School, Boston, Massachusetts
(Frank); Teva Pharmaceutical Industries, Frazer,
Pennsylvania (Stamler); Clinical Trials Coordination
Center, University of Rochester, Rochester, New
York (Kayson, Eberly, Goldstein); Department of
Neurology, Vanderbilt University Medical Center,
Nashville, Tennessee (Claassen); Department of
Neurology, Cooper University Hospital, Camden,
New Jersey (Colcher, Mallonee); CSD Biostatistics,
Tucson, Arizona (Davis); Department of Neurology,
University of Cincinnati, Cincinnati, Ohio (Duker);
The Center for Neurologic Health, Toledo, Ohio
(Elmer); Department of Neurology, The University
of Texas Medical School, Houston (Furr-Stimming);
South Shore Neurologic Associates, Islip, New York
(Gudesblatt); Department of Neurology, Baylor
College of Medicine, Houston, Texas (Hunter,
Jankovic); Department of Neurology, The Ohio
State University, Columbus (Kostyk); Rocky
Mountain Movement Disorders Center, Englewood,
Colorado (Kumar); Department of Neurology,
University of Sydney, Sydney, Australia (Loy);
Department of Statistics, University of Rochester,
Rochester, New York (Oakes); Department of
Neurology, Duke University, Durham, North
Carolina (Scott); Department of Neurology,
University of Alabama School of Medicine,
Birmingham (Sung); Department of Neurology,
Medical University of South Carolina, Charleston
(Vaughan); Department of Neurology, Virginia
Commonwealth University, Richmond (Testa).
Author Contributions: Drs Frank and Testa had full
access to all the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Frank, Stamler, Kayson,
Davis, Oakes, Vaughan, Testa.
Acquisition, analysis, or interpretation of data:
Frank, Stamler, Claassen, Colcher, Davis, Duker,
Elmer, Furr-Stimming, Gudesblatt, Hunter,
Jankovic, Kostyk, Kumar, Loy, Mallonee, Oakes,
Scott, Sung, Goldstein, Vaughan, Testa.
Drafting of the manuscript: Frank, Stamler, Colcher,
Davis, Duker, Furr-Stimming, Gudesblatt, Hunter,
Jankovic, Loy, Oakes, Vaughan, Testa.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Davis, Oakes.
Obtained funding: Frank.
Administrative, technical, or material support:
Kayson, Goldstein.
Study supervision: Frank, Stamler, Kayson,
Goldstein, Testa.
Conflict of Interest Disclosures: Dr Frank reported
receiving grants from the Huntington Study Group.
Dr Stamler reported being an employee of Auspex
Pharmaceuticals. Ms Kayson reported receiving
honoraria and funding for a meeting from Raptor
Pharmaceutical and serving as a consultant to
Pfizer Inc. Dr Davis reported serving as a consultant
for Auspex Pharmaceuticals. Dr Duker reported
receiving grants and nonfinancial support from HSG
on behalf of Auspex Pharmaceuticals during the
conduct of the study and other support from
Auspex Pharmaceuticals outside the submitted
work. Dr Furr-Stimming reported serving as a
consultant for Cynapsus and on the speakers’
bureau for Lundbeck (Xenazine) and Teva (Azilect).
Dr Jankovic reported receiving research and/or
training grants from Adamas Pharmaceuticals Inc,
Allergan Inc, CHDI Foundation, Civitas/Acorda
Therapeutics, Dystonia Medical Research
Foundation, Huntington Study Group, Ipsen
Limited, Kyowa Haako Kirin Pharma Inc, Lundbeck
Inc, Medtronic, Merz Pharmaceuticals, Michael J.
Fox Foundation for Parkinson Research, National
Institutes of Health, National Parkinson Foundation,
Parkinson Study Group, Pfizer, Prothena
Biosciences Inc, Psyadon Pharmaceuticals Inc, St.
Jude Medical, and Teva Pharmaceutical Industries
Ltd. Dr Jankovic reported serving as a consultant or
as an advisory committee member for Adamas
Pharmaceuticals Inc, Allergan Inc, and Teva
Pharmaceutical Industries Ltd. Dr Jankovic
reported receiving royalties from Cambridge,
Elsevier, Future Science Group, Hodder Arnold,
Lippincott Williams and Wilkins, and
Wiley-Blackwell and serving on editorial boards for
Medlink Neurology, Expert Review of
Neurotherapeutics, Neurology in Clinical Practice,
The Botulinum Journal, PeerJ, Therapeutic Advances
in Neurological Disorders, Neurotherapeutics,
Tremor and Other Hyperkinetic Movements, Journal
of Parkinson's Disease, and UpToDate. Dr Kostyk
reported receiving consultant fees from the

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 Research Original Investigation
National Institutes of Health and the US Food and
Drug Administration and has had meeting travel
costs covered through the Huntington's Study
Group and Pfizer Pharmaceuticals. Dr Kumar
reported receiving personal fees from Teva
Pharmaceuticals outside the submitted work. Dr
Mallonee reported receiving other support from
HSG on behalf of Auspex Pharmaceuticals during
the conduct of the study. Dr Oakes reported
receiving research support from Auspex for this and
another study of SD809 in Huntington disease
(HD), Vaccinex Inc and Prana Pharmaceuticals for
studies in HD, Biogen Inc for a study in Parkinson
disease, and the National Institutes of Health for
studies in HD and Parkinson disease and personal
honoraria from Raptor Pharmaceuticals and
Voyager Inc. Dr Sung reported receiving personal
fees from Lundbeck Inc. Dr Testa reported receiving
grants from the Huntington Study Group, Teva
Pharmaceuticals, and the CHDI Foundation and
other support from Auspex Pharmaceuticals and
Lundbeck Pharmaceuticals outside the submitted
work. No other disclosures are reported.
Funding/Support: This study was supported by
Auspex Pharmaceuticals, a wholly owned
subsidiary of Teva Pharmaceutical Industries Ltd.
Role of the Funder/Sponsor: Auspex
Pharmaceuticals aided in the design of the study;
provided input on the oversight, conduct, and
management of the study; played no role in the
collection of data but provided oversight with
management; was involved with but did not play
the primary role in analysis and interpretation of
the data; aided in the preparation of the manuscript
(figures, references, and formatting) and reviewed
content for intellectual property issues; and
provided approval of the final draft of the
manuscript. The decision to submit the manuscript
for publication was based on Huntington Study
Group principles with sponsor input through the
steering committee.
Group Information: The Huntington Study Group/
Alternatives for Reducing Chorea in Huntington
Disease Investigators are as follows: Joseph
Jankovic, MD, and Joohi Jimenez-Shahed, MD,
Parkinson’s Disease Center and Movement
Disorders Clinic, Houston, Texas; Sandra Kostyk,
MD, PhD, Ohio State University Medical Center,
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Tetrabenazine to Deutetrabenazine Conversion for Chorea Treatment
Columbus, Ohio; Daniel Claassen, MD, Department
of Neurology, Vanderbilt University, Nashville,
Tennessee; Rajeev Kumar, MD, and Vicki Segro,
MSN, C-ANP, Rocky Mountain Movement Disorders
Center, Englewood, Colorado; Clement Loy, MD,
Samuel Kim, MD, Elizabeth McCusker, Department
of Neurology, Westmead Hospital, Sydney,
Australia; William M. Mallonee, MD, Hereditary
Neurological Disease Centre, Wichita, Kansas;
Andrew Duker, MD, University of Cincinnati,
Cincinnati, Ohio; Fredy Revilla, MD, University
Neurology Inc, Cincinnati, Ohio; Lawrence Elmer,
MD, PhD, The University of Toledo
Gardner-Mcmaster Parkinson Center, Toledo, Ohio;
Burton Scott, MD, PhD, Duke Health Center, Duke
University, Durham, North Carolina; Patrick Hickey,
DO, Duke University Medical Center, Durham,
North Carolina; Erin Furr-Stimming, MD, University
of Texas at Houston, Houston; William Ondo, MD,
University of Texas Medical School at Houston,
Houston; Amy Colcher, MD, The Cooper University
Health System, Camden, New Jersey; Andrew
McGarry, MD, Cooper University Hospital, Camden,
New Jersey; and Mark Gudesblatt, MD, South Shore
Neurologic Associates, Patchoque, New York.
Additional Contributions: Administrative,
technical, and material support was provided by
Jacquelyn Whaley, MS, Sherry Weston, AAS
(University of Rochester, Rochester, New York), and
Nupur Patel (Teva Pharmaceuticals, Frazer,
Pennsylvania); these individuals received
compensation for their work. We thank the patients
and families who participated in this study.
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