Alternatives for Reducing Chorea in Huntington Disease

NCT ID: NCT01897896

Last Updated: 2021-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-12
• Study Completion Date: 2017-08-21

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SD-809

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

SD-809

Intervention Type: DRUG

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

Interventions

SD-809

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

Intervention Type: DRUG

Other Intervention Names

Deutetrabenazine

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Auspex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teva Medical Expert, MD

Role: STUDY_DIRECTOR

Teva Branded Pharmaceutical Products R&D, Inc.

Locations

Teva Investigational Site 057

Birmingham, Alabama, United States

Teva Investigational Site 038

Phoenix, Arizona, United States

Teva Investigational Site 298

Fayetteville, Arkansas, United States

Teva Investigational Site 052

Englewood, Colorado, United States

Teva Investigational Site 333

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

Teva Investigational Site 160

Gainesville, Florida, United States

Teva Investigational Site 014

Miami, Florida, United States

Teva Investigational Site 032

Atlanta, Georgia, United States

Teva Investigational Site 045

Indianapolis, Indiana, United States

Teva Investigational Site 024

Iowa City, Iowa, United States

Teva Investigational Site 029

Kansas City, Kansas, United States

Teva Investigational Site 083

Wichita, Kansas, United States

Teva Investigational Site 087

Louisville, Kentucky, United States

Teva Investigational Site 028

Baltimore, Maryland, United States

Teva Investigational Site 040

Boston, Massachusetts, United States

Teva Investigational Site 027

St Louis, Missouri, United States

Teva Investigational Site 194

Las Vegas, Nevada, United States

Teva Investigational Site 328

Camden, New Jersey, United States

Teva Investigational Site 026

New Brunswick, New Jersey, United States

Teva Investigational Site 037

Albany, New York, United States

Teva Investigational Site 002

New York, New York, United States

Teva Investigational Site 342

Patchogue, New York, United States

Teva Investigational Site 119

Durham, North Carolina, United States

Teva Investigational Site 089

Cincinnati, Ohio, United States

Teva Investigational Site 020

Columbus, Ohio, United States

Teva Investigational Site 093

Toledo, Ohio, United States

Teva Investigational Site 341

Tulsa, Oklahoma, United States

Teva Investigational Site 031

Nashville, Tennessee, United States

Teva Investigational Site 007

Houston, Texas, United States

Teva Investigational Site 199

Houston, Texas, United States

Teva Investigational Site 100

Salt Lake City, Utah, United States

Teva Investigational Site 137

Burlington, Vermont, United States

Teva Investigational Site 220

Kirkland, Washington, United States

Teva Investigational Site 096

Seattle, Washington, United States

Teva Investigational Site 054

Sydney, , Australia

Teva Investigational Site 098

Montreal, , Canada

Teva Investigational Site 231

Ottawa, , Canada

Teva Investigational Site 300

Toronto, , Canada

Countries

United States; Australia; Canada

References

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.

Reference Type: DERIVED

PMID: 39825184 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38557959 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36242718 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SD-809-C-16

Identifier Type: -

Identifier Source: org_study_id