First Time Use of SD-809 in Huntington Disease (First-HD)

This study is currently recruiting participants.
Verified March 2014 by Auspex Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Auspex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01795859
First received: February 20, 2013
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to determine whether SD-809 ER tablets are effective in the treatment of chorea associated with Huntington's Disease.


Condition Intervention Phase
Chorea
Drug: SD-809
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double Blind, Placebo Controlled Study of SD-809 Extended Release for the Treatment of Chorea Associated With Huntington Disease

Resource links provided by NLM:


Further study details as provided by Auspex Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Total Maximal Chorea Score (TMC) [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment Success at the end of therapy as measured by the Patient Global Impression of Change (PGIC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Treatment success at the end of therapy based on Clinical Global Impression of Change (CGIC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in Short Form 36 Health Survey (SF-36) Physical component summary score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in Berg Balance Test (BBT) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: June 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SD-809 ER Tablets Drug: SD-809
SD-809 extended release (ER) tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).
Other Name: d6-tetrabenazine
Placebo Comparator: SD-809 Placebo Drug: Placebo
Placebo tablets are available in three sizes, all of which are identical in size, shape and color (white).

Detailed Description:

This is a randomized, double blind, placebo controlled, parallel group study designed to evaluate the efficacy, safety and tolerability of SD-809 ER for the treatment of chorea associated with Huntington's Disease. Approximately 90 subjects will be randomized (1:1) into the study, with approximately 45 subjects receiving SD-809 ER and 45 subjects receiving placebo. The study will be conducted at approximately 30 centers in the U.S. and Canada.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is at least 18 years of age or the age of majority (whichever is older) at Screening.
  2. Subject has been diagnosed with manifest HD, as indicated by characteristic motor exam features and has an expanded CAG repeat (≥ 37) on Screening labs.
  3. Subject has a Total Maximal Chorea Score (TMC) ≥ 8 at Screening and Baseline. (Note: The Baseline TMC may be < 8 if the average of the Screening and Baseline scores is ≥ 8 and the difference between the Screening and Baseline scores is no more than 4).
  4. Subject has a Total Functional Capacity (TFC) score ≥ 5 at Screening.
  5. Subject is able to swallow study medication whole.
  6. Subject has provided written, informed consent or, if subject lacks the capacity to provide informed consent (as determined by an independent assessment by a qualified healthcare provider not directly involved in other study activities), a legally authorized representative (LAR) has provided written informed consent and the subject has provided assent.
  7. Female subjects of childbearing potential agree to use an acceptable method of contraception from screening through study completion. Female subjects of childbearing potential must be using one of the following acceptable birth control methods if sexually active:

    • IUD or intrauterine system in place for at least 3 months prior to screening;
    • Subject or partner using barrier method (e.g., condom, diaphragm, or cervical cap) with spermicide from screening through study completion;
    • Partner has a documented vasectomy > 6 months prior to enrollment.
    • Stable hormonal contraception (with approved oral, transdermal, or depot regimen) for at least 3 months prior to screening.
  8. The subject has a reliable caregiver who interacts with the patient on a daily basis, oversees study drug administration, assures attendance at study visits and participates in evaluations, as required.

    • Note: Subjects with a TFC score of 5-7 at Screening must have a live-in caregiver
    • Note: Subjects with a TFC score of 5-7 at Screening or those who enrolled with the consent of an LAR, must have caregivers present at all study visits.
    • Note: For subjects with a TFC score of 8-13 at Screening who did not require an LAR to provide informed consent, the caregiver must attend the Screening, Baseline and Weeks 4, 9 and 12 Visits. Caregivers will be encouraged to attend other visits.
  9. Subject is able to ambulate without assistance for at least 20 yards (Note: The use of assistive devices (i.e., walker, cane) is permitted during ambulation).

Exclusion Criteria:

  1. Subject has a serious untreated or under-treated psychiatric illness, such as depression, at Screening or Baseline.

    • Note: Subjects receiving antidepressant therapy may be enrolled if on a stable dose for at least 8 weeks before Screening.

  2. Subject has active suicidal ideation at Screening or Baseline.
  3. Subject has history of any of the following suicidal thoughts or behavior at Screening or Baseline:

    • Previous intent to act on suicidal ideation with a specific plan (positive answer to question 5 on C-SSRS), irrespective of level of ambivalence at the time of suicidal thought
    • Previous preparatory acts or behavior
    • A previous actual, interrupted or aborted suicide attempt
  4. Subject has a score ≥11 on the depression subscale of the Hospital Anxiety and Depression Scale (HADS) at Screening or Baseline.
  5. Subject has an unstable or serious medical or psychiatric illness at Screening or Baseline.
  6. Subject has been previously exposed to tetrabenazine.
  7. Subject 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
  8. Subject has a score of ≥11 on the Swallowing Disturbance Questionnaire (SDQ) at Screening.
  9. Subject has a Unified Parkinson's Disease Rating Scale (UPDRS) dysarthria score of ≥3 at Screening.
  10. Subject requires treatment with drugs known to prolong the QT interval. Note:

    • Quetiapine (Seroquel) is not allowed.
    • Escitalopram (Lexapro or Cipralex) is allowed when administered according to approved labeling.
    • Citalopram (Celexa) is allowed when administered according to approved labeling.
  11. Subject has a QTcF value >450 ms (males) or >460 ms (females), or >480 ms (with right bundle branch block) on 12-lead ECG at Screening.

    • Note: Subjects with left bundle branch block are not eligible

  12. Subject has evidence of hepatic impairment at Screening, as indicated by:

    • AST or ALT >2.5 times the upper limit of normal.
    • Alkaline phosphatase (ALP) or total bilirubin (TBil) >2 times the upper limit of normal (ULN)

      • Note: Subjects with Gilbert's Syndrome are eligible to participate if approved by the medical monitor.
      • Note: Subjects with abnormalities in two or more of these analytes (AST, ALT, ALP, TBil) must be approved by the medical monitor in order to be enrolled.
    • Prothrombin time > 4 sec prolonged.
    • Positive Hepatitis B surface antigen (HBsAg).
  13. Subject has evidence of significant renal impairment at Screening, indicated by a creatinine clearance <50 mL/min, as estimated by the Cockcroft-Gault formula.
  14. Subject has known allergy to any of the components of study medication.
  15. Subject has participated in an investigational drug or device trial within 30 days (or 5 drug half-lives) of Screening, whichever is longer.
  16. Subject is pregnant or breast-feeding at Screening or Baseline.
  17. Subject acknowledges present use of illicit drugs at Screening.
  18. Subject has a history of alcohol or substance abuse in the previous 12 months, as defined in the DSM-IV, or subject is unable to refrain from substance abuse throughout the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01795859

  Show 27 Study Locations
Sponsors and Collaborators
Auspex Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Auspex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01795859     History of Changes
Other Study ID Numbers: SD-809-C-15
Study First Received: February 20, 2013
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Auspex Pharmaceuticals, Inc.:
Huntington disease
Chorea
Tetrabenazine

Additional relevant MeSH terms:
Huntington Disease
Chorea
Dyskinesias
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Basal Ganglia Diseases
Brain Diseases
Dementia
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Tetrabenazine
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 15, 2014