Alternatives for Reducing Chorea in Huntington Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 15 November 2021
• Main ID: NCT01897896
• Date of registration: 14/06/2013
• Prospective Registration: Yes
• Primary sponsor: Auspex Pharmaceuticals, Inc.
• Public title: Alternatives for Reducing Chorea in Huntington Disease ARC-HD
• Scientific title: An Open-Label, Long Term Safety Study of SD-809 ER in Subjects With Chorea Associated With Huntington Disease
• Date of first enrolment: November 12, 2013
• Target sample size: 119
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01897896
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Canada, United States

Contacts

• Name: Teva Medical Expert, MD
• Affiliation: Teva Branded Pharmaceutical Products R&D, Inc.

Key inclusion & exclusion criteria

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.

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Chorea Associated With Huntington Disease

Intervention(s)

Drug: SD-809

Primary Outcome(s)

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 [Time Frame: Baseline to follow-up visit (up to approximately 3 years 9 months)]

Rollover Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Titration [Time Frame: Day 1 to end of Week 8]

Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Long Term Stable Dose Treatment [Time Frame: Week 8 to follow-up visit (up to approximately 3 years 9 months)]

Switch Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Dose Adjustment [Time Frame: Day 1 to end of Week 4]

Secondary Outcome(s)

Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes Mean Corpuscular Volume) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in Heart Rate at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in UHDRS Motor Assessment: Total Motor Score (TMS) at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in UHDRS Total Functional Capacity (TFC) Score at Week 132 [Time Frame: Baseline, Week 132]

Change From Week 8 in UHDRS Motor Assessment: TMC Score at Week 171 [Time Frame: Week 8, Week 171]

Change From Baseline in Body Temperature at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Aspartate Aminotransferase and Lactate Dehydrogenase) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bilirubin, Creatinine, Direct Bilirubin, and Urate) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in Respiration Rate at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) -Dysarthria Score at Week 171 [Time Frame: Baseline, Week 171]

Number of Participants With Clinically Significant Abnormalities in ECG Parameters [Time Frame: Baseline, Week 8]

Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) [Time Frame: Baseline up to 1-week follow-up visit (up to approximately 3 years 9 months)]

Change From Baseline in Clinical Laboratory Hematology Parameter (Hematocrit) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in UHDRS Motor Assessment: Total Maximal Chorea (TMC) Score at Week 171 [Time Frame: Baseline, Week 171]

Duration of Time to Achieve a Stable Dose of SD-809 ER [Time Frame: 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)]

Change From Baseline in Clinical Laboratory Serum Chemistry Parameter (Creatinine Clearance) at Week 106 [Time Frame: Baseline, Week 106]

Change From Baseline in UHDRS Cognitive Assessment Score at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in UHDRS Functional Assessment Score at Week 28 [Time Frame: Baseline, Week 28]

Electrocardiogram (ECG) Parameter Value (Heart Rate) at Baseline and Week 8 [Time Frame: Baseline, Week 8]

Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Assessment Score at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score at Week 171 [Time Frame: Baseline, Week 171]

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 [Time Frame: Baseline, Week 158]

Change From Baseline in Barnes Akathisia Rating Scale (BARS) Summary Score at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in Blood Pressure at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in Clinical Laboratory Hematology Parameter (Hemoglobin) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in Clinical Laboratory Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Alanine Aminotransferase and Alkaline Phosphatase) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score at Week 171 [Time Frame: Baseline, Week 171]

Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Protein and Albumin) at Week 158 [Time Frame: Baseline, Week 158]

Change From Baseline in UHDRS Independence Scale Score at Week 28 [Time Frame: Baseline, Week 28]

Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Behavior Score at Week 171 [Time Frame: Baseline, Week 171]

Change From Week 8 in UHDRS Motor Assessment: TMS at Week 171 [Time Frame: Week 8, Week 171]

ECG Parameter Value (PR Interval, QRS Duration, QT Interval, QTcF) at Baseline and Week 8 [Time Frame: Baseline, Week 8]

Secondary ID(s)

SD-809-C-16

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/04/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01897896