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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01897896




Registration number
NCT01897896
Ethics application status
Date submitted
14/06/2013
Date registered
12/07/2013
Date last updated
9/11/2021

Titles & IDs
Public title
Alternatives for Reducing Chorea in Huntington Disease
Scientific title
An Open-Label, Long Term Safety Study of SD-809 ER in Subjects With Chorea Associated With Huntington Disease
Secondary ID [1] 0 0
SD-809-C-16
Universal Trial Number (UTN)
Trial acronym
ARC-HD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chorea Associated With Huntington Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SD-809

Experimental: Rollover Cohort: SD-809 ER - Participants who completed study SD-809-C-15 (NCT01795859, including 1-week washout period and Week 13 evaluation), will receive 6 milligrams (mg) SD-809 ER tablet once daily as a starting dose in this study. Dose titration will be continued through Week 8 to optimize dose. Dose of SD-809 ER can be adjusted weekly in increments of 6 milligrams per day (mg/day) (6 or 12 mg/day after a total daily dose of 48 mg is reached) based on chorea control and adverse events. Daily doses of SD-809 ER 12 mg and higher will be administered twice daily. Maximum total daily dose of SD-809 ER will be 72 mg/day (36 mg twice daily), unless participant is receiving a strong CYP2D6 inhibitor(such as, paroxetine, buproprion, fluoxetine), in which case maximum total daily dose will be 42 mg (21 mg twice daily). Long-term treatment with SD-809 ER at a stable dose (further dose adjustments are permitted, if clinically indicated) will be continued until SD-809 ER become commercially available in United States.

Experimental: Switch Cohort: SD-809 ER - Participants who were receiving an approved dosing regimen of tetrabenazine for at least 8 weeks prior to screening, will be converted overnight from their existing tetrabenazine regimen to SD-809 ER regimen to achieve targeted steady-state area under the curve (AUC) of total (alpha+beta)- Dihydrotetrabenazine (HTBZ) metabolites that is predicted to be comparable to that of participant's prior tetrabenazine regimen. Participants will remain on initial dose of SD-809 ER through Week 1. Dose adjustment will be continued through Week 4 to optimize the dose. Dose of SD-809 ER can be adjusted weekly (upward or downward) in increments of 6 mg per day (6 mg/day or 12 mg/day after a total daily dose of 48 mg is reached), based on chorea control and treatment regimen tolerability. Long-term treatment with SD-809 ER at a stable dose (although further dose adjustments are permitted, if clinically indicated) will be continued until SD-809 ER become commercially available in United States.


Treatment: Drugs: SD-809
SD-809 tablets will be provided in dose strengths of 6, 9 and 12 mg.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Entire Treatment Period
Timepoint [1] 0 0
Baseline to follow-up visit (up to approximately 3 years 9 months)
Primary outcome [2] 0 0
Rollover Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Titration
Timepoint [2] 0 0
Day 1 to end of Week 8
Primary outcome [3] 0 0
Switch Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Dose Adjustment
Timepoint [3] 0 0
Day 1 to end of Week 4
Primary outcome [4] 0 0
Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Long Term Stable Dose Treatment
Timepoint [4] 0 0
Week 8 to follow-up visit (up to approximately 3 years 9 months)
Secondary outcome [1] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets) at Week 158
Timepoint [1] 0 0
Baseline, Week 158
Secondary outcome [2] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes Mean Corpuscular Volume) at Week 158
Timepoint [2] 0 0
Baseline, Week 158
Secondary outcome [3] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes) at Week 158
Timepoint [3] 0 0
Baseline, Week 158
Secondary outcome [4] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameter (Hematocrit) at Week 158
Timepoint [4] 0 0
Baseline, Week 158
Secondary outcome [5] 0 0
Change From Baseline in Clinical Laboratory Hematology Parameter (Hemoglobin) at Week 158
Timepoint [5] 0 0
Baseline, Week 158
Secondary outcome [6] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Alanine Aminotransferase and Alkaline Phosphatase) at Week 158
Timepoint [6] 0 0
Baseline, Week 158
Secondary outcome [7] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Aspartate Aminotransferase and Lactate Dehydrogenase) at Week 158
Timepoint [7] 0 0
Baseline, Week 158
Secondary outcome [8] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Cholesterol, Glucose, Magnesium, Phosphate, Potassium, Sodium, Triglycerides) at Week 158
Timepoint [8] 0 0
Baseline, Week 158
Secondary outcome [9] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Protein and Albumin) at Week 158
Timepoint [9] 0 0
Baseline, Week 158
Secondary outcome [10] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameter (Creatinine Clearance) at Week 106
Timepoint [10] 0 0
Baseline, Week 106
Secondary outcome [11] 0 0
Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bilirubin, Creatinine, Direct Bilirubin, and Urate) at Week 158
Timepoint [11] 0 0
Baseline, Week 158
Secondary outcome [12] 0 0
Change From Baseline in Blood Pressure at Week 171
Timepoint [12] 0 0
Baseline, Week 171
Secondary outcome [13] 0 0
Change From Baseline in Heart Rate at Week 171
Timepoint [13] 0 0
Baseline, Week 171
Secondary outcome [14] 0 0
Change From Baseline in Respiration Rate at Week 171
Timepoint [14] 0 0
Baseline, Week 171
Secondary outcome [15] 0 0
Change From Baseline in Body Temperature at Week 171
Timepoint [15] 0 0
Baseline, Week 171
Secondary outcome [16] 0 0
Electrocardiogram (ECG) Parameter Value (Heart Rate) at Baseline and Week 8
Timepoint [16] 0 0
Baseline, Week 8
Secondary outcome [17] 0 0
ECG Parameter Value (PR Interval, QRS Duration, QT Interval, QTcF) at Baseline and Week 8
Timepoint [17] 0 0
Baseline, Week 8
Secondary outcome [18] 0 0
Number of Participants With Clinically Significant Abnormalities in ECG Parameters
Timepoint [18] 0 0
Baseline, Week 8
Secondary outcome [19] 0 0
Duration of Time to Achieve a Stable Dose of SD-809 ER
Timepoint [19] 0 0
From Day 1 until the first day at which the participant was taking the dose level they were receiving at Week 8 (up to maximum 1284 days)
Secondary outcome [20] 0 0
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) -Dysarthria Score at Week 171
Timepoint [20] 0 0
Baseline, Week 171
Secondary outcome [21] 0 0
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Summary Score at Week 171
Timepoint [21] 0 0
Baseline, Week 171
Secondary outcome [22] 0 0
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Assessment Score at Week 171
Timepoint [22] 0 0
Baseline, Week 171
Secondary outcome [23] 0 0
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score at Week 171
Timepoint [23] 0 0
Baseline, Week 171
Secondary outcome [24] 0 0
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score at Week 171
Timepoint [24] 0 0
Baseline, Week 171
Secondary outcome [25] 0 0
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 171
Timepoint [25] 0 0
Baseline, Week 171
Secondary outcome [26] 0 0
Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS)
Timepoint [26] 0 0
Baseline up to 1-week follow-up visit (up to approximately 3 years 9 months)
Secondary outcome [27] 0 0
Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 171
Timepoint [27] 0 0
Baseline, Week 171
Secondary outcome [28] 0 0
Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Behavior Score at Week 171
Timepoint [28] 0 0
Baseline, Week 171
Secondary outcome [29] 0 0
Change From Baseline in UHDRS Functional Assessment Score at Week 28
Timepoint [29] 0 0
Baseline, Week 28
Secondary outcome [30] 0 0
Change From Baseline in UHDRS Independence Scale Score at Week 28
Timepoint [30] 0 0
Baseline, Week 28
Secondary outcome [31] 0 0
Change From Baseline in UHDRS Total Functional Capacity (TFC) Score at Week 132
Timepoint [31] 0 0
Baseline, Week 132
Secondary outcome [32] 0 0
Change From Baseline in UHDRS Cognitive Assessment Score at Week 171
Timepoint [32] 0 0
Baseline, Week 171
Secondary outcome [33] 0 0
Change From Baseline in UHDRS Motor Assessment: Total Maximal Chorea (TMC) Score at Week 171
Timepoint [33] 0 0
Baseline, Week 171
Secondary outcome [34] 0 0
Change From Week 8 in UHDRS Motor Assessment: TMC Score at Week 171
Timepoint [34] 0 0
Week 8, Week 171
Secondary outcome [35] 0 0
Change From Baseline in UHDRS Motor Assessment: Total Motor Score (TMS) at Week 171
Timepoint [35] 0 0
Baseline, Week 171
Secondary outcome [36] 0 0
Change From Week 8 in UHDRS Motor Assessment: TMS at Week 171
Timepoint [36] 0 0
Week 8, Week 171

Eligibility
Key inclusion criteria
- Participant is at least 18 years of age or the age of majority (whichever is older) at
Screening.

- Participant has been diagnosed with manifest HD, as indicated by characteristic motor
exam features, and has a documented expanded cytosine adenine guanine (CAG) repeat
(greater than or equal to >= [37]) at or before Screening.

- Participant meets either of the following:

1. Has successfully completed participation in the First-HD Study (SD-809-C-15) or

2. Has been receiving an Food and Drug Administration (FDA)-approved dose of
tetrabenazine that has been stable for >=8 weeks before Screening and is
providing a therapeutic benefit for control of chorea.

- Participant has a Total Functional Capacity (TFC) score >=5 at Screening.

- Participant is able to swallow study medication whole.

- Participant has provided written, informed consent or, a legally authorized
representative (LAR) has provided written informed consent and the subject has
provided assent.

- Participant has provided a Research Advance Directive.

- Female participants of childbearing potential agree to use an acceptable method of
contraception from screening through study completion.

- The participant has a reliable caregiver who interacts with the participant on a daily
basis, oversees study drug administration, assures attendance at study visits and
participates in evaluations, as required.

- Participant is able to ambulate without assistance for at least 20 yards (Note: The
use of assistive devices (such as; walker, cane) are permitted during ambulation).

- Has sufficient reading skills to comprehend the participant completed rating scales.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participant has a serious untreated or under-treated psychiatric illness, such as
depression, at Screening or Baseline.

- Participant has active suicidal ideation at Screening or Baseline.

- Participant has history of suicidal behavior at Screening or Baseline.

- Participant has evidence for depression at Baseline.

- Participant has an unstable or serious medical illness at Screening or Baseline.

- Participant has received tetrabenazine within 7 days of Baseline (Rollover
participants only).

- Participant has received any of the following concomitant medications within 30 days
of Screening or Baseline: Antipsychotics, Metoclopramide, Monoamine oxidase inhibitors
(MAOI), Levodopa or dopamine agonists, Reserpine, Amantadine, Memantine (Rollover
participants only)

- Switch participants may receive Memantine if on a stable, approved dose for at least
30 days

- Participant has significantly impaired swallowing function at Screening or Baseline.

- Participant has significantly impaired speaking at Screening or Baseline.

- Participant requires treatment with drugs known to prolong the QT interval.

- Participant has prolonged QT interval on 12-lead electrocardiogram (ECG) at Screening.

- Participant has evidence of hepatic impairment at Screening.

- Participant has evidence of significant renal impairment at Screening.

- Participant has known allergy to any of the components of study medication.

- Participant has participated in an investigational drug or device trial other than
SD-809-C-15 within 30 days (or 5 drug half-lives) of Screening, whichever is longer.

- Participant is pregnant or breast-feeding at Screening or Baseline.

- Participant acknowledges present use of illicit drugs at Screening or Baseline.

- Participant has a history of alcohol or substance abuse in the previous 12 months.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/11/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/08/2017
Sample size
Target
Accrual to date
Final
119
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Teva Investigational Site 054 - Sydney
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment outside Australia
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Massachusetts
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Oklahoma
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Canada
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Montreal
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Ottawa
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Canada
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Toronto

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Auspex Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of
SD-809 extended release (ER) in participants switching from tetrabenazine to SD-809 ER. In
addition, the safety and tolerability of long-term treatment with SD-809 ER will be assessed
in "Switch" participants as well as "Rollover" participants completing a randomized, double
blind, placebo-controlled study of SD-809 ER.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01897896
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Teva Medical Expert, MD
Address 0 0
Teva Branded Pharmaceutical Products R&D, Inc.
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries