Alternatives for Reducing Chorea in Huntington Disease

NCT01897896 | Completed Phase 3 Results FDA Drug

• 1 other identifier: SD-809-C-16
• Study Type: interventional
• Target: 119
• Locations: 3 countries
• Sites: 38

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.

Conditions

Chorea Associated With Huntington Disease

Keywords

Chorea; Huntington Disease

Outcome Measures

Primary Outcomes (4)

• 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

  An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=inability to carry out usual activities. Drug-related TEAEs: TEAEs with possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  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

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Day 1 to end of Week 8

• Switch Cohort: Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Dose Adjustment

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Day 1 to end of Week 4

• Number of Participants With TEAEs, Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal During Long Term Stable Dose Treatment

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AEs=inability to carry out usual activities. Drug-related TEAEs: TEAEs with a possible, probable, definite, or missing relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: events that 1) began after treatment with study drug in current study and that were not present at baseline or 2) if present at baseline, had worsened in severity. Any TEAEs included both serious and non-serious TEAEs. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

  Week 8 to follow-up visit (up to approximately 3 years 9 months)

Secondary Outcomes (36)

• Change From Baseline in Clinical Laboratory Hematology Parameters (Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets) at Week 158

  Baseline, Week 158

• Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes Mean Corpuscular Volume) at Week 158

  Baseline, Week 158

• Change From Baseline in Clinical Laboratory Hematology Parameter (Erythrocytes) at Week 158

  Baseline, Week 158

• Change From Baseline in Clinical Laboratory Hematology Parameter (Hematocrit) at Week 158

  Baseline, Week 158

• Change From Baseline in Clinical Laboratory Hematology Parameter (Hemoglobin) at Week 158

  Baseline, Week 158

Study Arms (2)

Rollover Cohort: SD-809 ER

EXPERIMENTAL

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.

Drug: SD-809

Switch Cohort: SD-809 ER

EXPERIMENTAL

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.

Drug: SD-809

Interventions

SD-809 DRUG

SD-809 tablets will be provided in dose strengths of 6, 9 and 12 mg.

Also known as: Deutetrabenazine

Rollover Cohort: SD-809 ER; Switch Cohort: SD-809 ER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Auspex Pharmaceuticals, Inc.: lead

Study Sites (38)

Teva Investigational Site 057

Birmingham, Alabama, 35233, United States

Location

Teva Investigational Site 038

Phoenix, Arizona, 85013, United States

Location

Teva Investigational Site 298

Fayetteville, Arkansas, 72703, United States

Location

Teva Investigational Site 052

Englewood, Colorado, 80113, United States

Location

Teva Investigational Site 333

Washington D.C., District of Columbia, 20007, United States

Location

Teva Investigational Site 160

Gainesville, Florida, 32607, United States

Location

Teva Investigational Site 014

Miami, Florida, 33136, United States

Location

Teva Investigational Site 032

Atlanta, Georgia, 30329, United States

Location

Teva Investigational Site 045

Indianapolis, Indiana, 46202, United States

Location

Teva Investigational Site 024

Iowa City, Iowa, 52242, United States

Location

Teva Investigational Site 029

Kansas City, Kansas, 66160, United States

Location

Teva Investigational Site 083

Wichita, Kansas, 67226, United States

Location

Teva Investigational Site 087

Louisville, Kentucky, 40202, United States

Location

Teva Investigational Site 028

Baltimore, Maryland, 21287, United States

Location

Teva Investigational Site 040

Boston, Massachusetts, 02118, United States

Location

Teva Investigational Site 027

St Louis, Missouri, 63110, United States

Location

Teva Investigational Site 194

Las Vegas, Nevada, 89102, United States

Location

Teva Investigational Site 328

Camden, New Jersey, 08103, United States

Location

Teva Investigational Site 026

New Brunswick, New Jersey, 08901, United States

Location

Teva Investigational Site 037

Albany, New York, 12208, United States

Location

Teva Investigational Site 002

New York, New York, 10032, United States

Location

Teva Investigational Site 342

Patchogue, New York, 11772, United States

Location

Teva Investigational Site 119

Durham, North Carolina, 27705, United States

Location

Teva Investigational Site 089

Cincinnati, Ohio, 45267, United States

Location

Teva Investigational Site 020

Columbus, Ohio, 43210, United States

Location

Teva Investigational Site 093

Toledo, Ohio, 43614-2598, United States

Location

Teva Investigational Site 341

Tulsa, Oklahoma, 74136, United States

Location

Teva Investigational Site 031

Nashville, Tennessee, 37232-2551, United States

Location

Teva Investigational Site 007

Houston, Texas, 77030, United States

Location

Teva Investigational Site 199

Houston, Texas, 77030, United States

Location

Teva Investigational Site 100

Salt Lake City, Utah, 84108, United States

Location

Teva Investigational Site 137

Burlington, Vermont, 05401, United States

Location

Teva Investigational Site 220

Kirkland, Washington, 98034, United States

Location

Teva Investigational Site 096

Seattle, Washington, 98108, United States

Location

Teva Investigational Site 054

Sydney, 2145, Australia

Location

Teva Investigational Site 098

Montreal, H2L4M1, Canada

Location

Teva Investigational Site 231

Ottawa, K1G 3G4, Canada

Location

Teva Investigational Site 300

Toronto, M2K 1E1, Canada

Location

Related Publications (3)

• Frank S, Testa CM, Goldstein J, Kayson E, Leavitt BR, Oakes D, O'Neill C, Whaley J, Gross N, Chaijale N, Barash S, Gordon MF; Huntington Study Group/ARC-HD Investigators and Coordinators. Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease. CNS Drugs. 2025 Feb;39(2):185-195. doi: 10.1007/s40263-024-01139-3. Epub 2025 Jan 18.

  PMID: 39825184 DERIVED

• Frank S, Anderson KE, Fernandez HH, Hauser RA, Claassen DO, Stamler D, Factor SA, Jimenez-Shahed J, Barkay H, Wilhelm A, Alexander JK, Chaijale N, Barash S, Savola JM, Gordon MF, Chen M. Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated with Huntington Disease. Neurol Ther. 2024 Jun;13(3):655-675. doi: 10.1007/s40120-024-00600-1. Epub 2024 Apr 1.

  PMID: 38557959 DERIVED

• 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.

  PMID: 36242718 DERIVED

MeSH Terms

Conditions

Chorea; Huntington Disease

Interventions

deutetrabenazine

Condition Hierarchy (Ancestors)

Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Basal Ganglia Diseases; Brain Diseases; Dementia; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: July 12, 2013
• Study Start: November 12, 2013
• Primary Completion: August 21, 2017
• Study Completion: August 21, 2017
• Last Updated: November 9, 2021
• Results First Posted: April 16, 2019

Record last verified: 2021-11

Locations

US (34); AU (1); CA (3)