Alternatives for Reducing Chorea in Huntington Disease (ARC-HD)

Auspex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Chorea Associated With Huntington Disease

Treatments: Drug: SD-809

Study type: Interventional

Funder types: Industry

Identifiers

NCT01897896

SD-809-C-16

Details and patient eligibility

About

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.

Enrollment: 119 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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119 participants in 2 patient groups

Rollover Cohort: SD-809 ER

Experimental group

Description:

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.

Treatment:

Drug: SD-809

Switch Cohort: SD-809 ER

Experimental group

Description:

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:

Drug: SD-809