Clinical trial NCT01897896: Alternatives for Reducing Chorea in Huntington Disease
Official title: An Open-Label, Long Term Safety Study of SD-809 ER in Subjects With Chorea Associated With Huntington Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chorea Associated With Huntington Disease
Keywords: Chorea
Huntington Disease
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-12
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Baseline to follow-up visit (up to approximately 3 years 9 months)
measure: Rollover Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Titration
timeFrame: Day 1 to end of Week 8
measure: Switch Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Dose Adjustment
timeFrame: Day 1 to end of Week 4
measure: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Long Term Stable Dose Treatment
timeFrame: Week 8 to follow-up visit (up to approximately 3 years 9 months)
Secondary outcomes:
measure: Change From Baseline in Clinical Laboratory Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets) at Week 158
timeFrame: Baseline, Week 158
measure: Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes Mean Corpuscular Volume) at Week 158
timeFrame: Baseline, Week 158
measure: Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes) at Week 158
timeFrame: Baseline, Week 158
measure: Change From Baseline in Clinical Laboratory Hematology Parameter (Hematocrit) at Week 158
timeFrame: Baseline, Week 158
measure: Change From Baseline in Clinical Laboratory Hematology Parameter (Hemoglobin) at Week 158
timeFrame: Baseline, Week 158
measure: Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Alanine Aminotransferase and Alkaline Phosphatase) at Week 158
timeFrame: Baseline, Week 158
measure: Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Aspartate Aminotransferase and Lactate Dehydrogenase) at Week 158
timeFrame: Baseline, Week 158
measure: 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
timeFrame: Baseline, Week 158
measure: Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Protein and Albumin) at Week 158
timeFrame: Baseline, Week 158
measure: Change From Baseline in Clinical Laboratory Serum Chemistry Parameter (Creatinine Clearance) at Week 106
timeFrame: Baseline, Week 106
measure: Change From Baseline in Clinical Laboratory Serum Chemistry Parameters (Bilirubin, Creatinine, Direct Bilirubin, and Urate) at Week 158
timeFrame: Baseline, Week 158
measure: Change From Baseline in Blood Pressure at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Heart Rate at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Respiration Rate at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Body Temperature at Week 171
timeFrame: Baseline, Week 171
measure: Electrocardiogram (ECG) Parameter Value (Heart Rate) at Baseline and Week 8
timeFrame: Baseline, Week 8
measure: ECG Parameter Value (PR Interval, QRS Duration, QT Interval, QTcF) at Baseline and Week 8
timeFrame: Baseline, Week 8
measure: Number of Participants With Clinically Significant Abnormalities in ECG Parameters
timeFrame: Baseline, Week 8
measure: Duration of Time to Achieve a Stable Dose of SD-809 ER
timeFrame: 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)
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) -Dysarthria Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Barnes Akathisia Rating Scale (BARS) Summary Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Assessment Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Anxiety Subscale Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 171
timeFrame: Baseline, Week 171
measure: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to 1-week follow-up visit (up to approximately 3 years 9 months)
measure: Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Behavior Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in UHDRS Functional Assessment Score at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in UHDRS Independence Scale Score at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in UHDRS Total Functional Capacity (TFC) Score at Week 132
timeFrame: Baseline, Week 132
measure: Change From Baseline in UHDRS Cognitive Assessment Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Baseline in UHDRS Motor Assessment: Total Maximal Chorea (TMC) Score at Week 171
timeFrame: Baseline, Week 171
measure: Change From Week 8 in UHDRS Motor Assessment: TMC Score at Week 171
timeFrame: Week 8, Week 171
measure: Change From Baseline in UHDRS Motor Assessment: Total Motor Score (TMS) at Week 171
timeFrame: Baseline, Week 171
measure: Change From Week 8 in UHDRS Motor Assessment: TMS at Week 171
timeFrame: Week 8, Week 171
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 057
state: Alabama
city: Phoenix
country: United States
facility: Teva Investigational Site 038
state: Arizona
city: Fayetteville
country: United States
facility: Teva Investigational Site 298
state: Arkansas
city: Englewood
country: United States
facility: Teva Investigational Site 052
state: Colorado
city: Washington
country: United States
facility: Teva Investigational Site 333
state: District of Columbia
city: Gainesville
country: United States
facility: Teva Investigational Site 160
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 014
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 032
state: Georgia
city: Indianapolis
country: United States
facility: Teva Investigational Site 045
state: Indiana
city: Iowa City
country: United States
facility: Teva Investigational Site 024
state: Iowa
city: Kansas City
country: United States
facility: Teva Investigational Site 029
state: Kansas
city: Wichita
country: United States
facility: Teva Investigational Site 083
state: Kansas
city: Louisville
country: United States
facility: Teva Investigational Site 087
state: Kentucky
city: Baltimore
country: United States
facility: Teva Investigational Site 028
state: Maryland
city: Boston
country: United States
facility: Teva Investigational Site 040
state: Massachusetts
city: Saint Louis
country: United States
facility: Teva Investigational Site 027
state: Missouri
city: Las Vegas
country: United States
facility: Teva Investigational Site 194
state: Nevada
city: Camden
country: United States
facility: Teva Investigational Site 328
state: New Jersey
city: New Brunswick
country: United States
facility: Teva Investigational Site 026
state: New Jersey
city: Albany
country: United States
facility: Teva Investigational Site 037
state: New York
city: New York
country: United States
facility: Teva Investigational Site 002
state: New York
city: Patchogue
country: United States
facility: Teva Investigational Site 342
state: New York
city: Durham
country: United States
facility: Teva Investigational Site 119
state: North Carolina
city: Cincinnati
country: United States
facility: Teva Investigational Site 089
state: Ohio
city: Columbus
country: United States
facility: Teva Investigational Site 020
state: Ohio
city: Toledo
country: United States
facility: Teva Investigational Site 093
state: Ohio
city: Tulsa
country: United States
facility: Teva Investigational Site 341
state: Oklahoma
city: Nashville
country: United States
facility: Teva Investigational Site 031
state: Tennessee
city: Houston
country: United States
facility: Teva Investigational Site 007
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 199
state: Texas
city: Salt Lake City
country: United States
facility: Teva Investigational Site 100
state: Utah
city: Burlington
country: United States
facility: Teva Investigational Site 137
state: Vermont
city: Kirkland
country: United States
facility: Teva Investigational Site 220
state: Washington
city: Seattle
country: United States
facility: Teva Investigational Site 096
state: Washington
city: Sydney
country: Australia
facility: Teva Investigational Site 054
city: Montreal
country: Canada
facility: Teva Investigational Site 098
city: Ottawa
country: Canada
facility: Teva Investigational Site 231
city: Toronto
country: Canada
facility: Teva Investigational Site 300
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: Frank S, Testa C, Edmondson MC, Goldstein J, Kayson E, Leavitt BR, Oakes D, O'Neill C, Vaughan C, Whaley J, Gross N, Gordon MF, Savola JM; Huntington Study Group/ARC-HD Investigators and Coordinators. The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open-Label Extension Study. CNS Drugs. 2022 Nov;36(11):1207-1216. doi: 10.1007/s40263-022-00956-8. Epub 2022 Oct 15.