Trial record 4 of 109 for:    Chorea

Alternatives for Reducing Chorea in HD (ARC-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:
NCT01897896
First received: June 14, 2013
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the safety and tolerability of titration and maintenance therapy of SD-809 ER, safety and tolerability of switching subjects from tetrabenazine to SD-809 ER and to evaluate the pharmacokinetics of tetrabenazine, SD-809 and the respective metabolites in subjects switching from tetrabenazine to SD-809 ER.


Condition Intervention Phase
Chorea Associated With Huntington Disease
Drug: SD-809 ER
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Long Term Safety Study of SD-809 ER in Patients With Chorea Associated With Huntington Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall incidence of adverse events (AEs), serious AEs, severe AEs, drug related AEs, AEs leading to withdrawal [ Time Frame: Up to 58 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events (AEs), serious AEs, severe AEs, drug related AEs, AEs leading to withdrawal during the titration period in Rollover subjects [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events (AEs), serious AEs, severe AEs, drug related AEs, AEs leading to withdrawal during the dose adjustment period in Switch subjects [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events (AEs), serious AEs, severe AEs, drug related AEs, AEs leading to withdrawal during long term treatment [ Time Frame: From Week 3 to Week 54 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes from baseline in clinical laboratory parameters (hematology, chemistry and urinalysis) [ Time Frame: Up to 58 weeks ] [ Designated as safety issue: No ]
  • Changes from baseline in UHDRS, UPDRS (dysarthria), BARS, HADS, ESS, C-SSR, and MoCA [ Time Frame: Up to 58 weeks ] [ Designated as safety issue: No ]
  • Changes from baseline in vital signs [ Time Frame: Up to 58 weeks ] [ Designated as safety issue: No ]
  • Changes from baseline in ECG parameters and abnormal findings [ Time Frame: Up to 58 weeks ] [ Designated as safety issue: No ]
  • Duration of time to achieve stable dosing of SD-809 ER [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 116
Study Start Date: July 2013
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Switch Subjects
Switch subjects are those who are currently receiving stable doses of tetrabenazine for treatment of chorea associated with HD and convert to SD-809 ER based on an algorithm designed to achieve comparable exposure to total (α+β)-HTBZ metabolites.
Drug: SD-809 ER

SD-809 extended release (ER) tablets will be provided in dose strengths of 6, 9 and 12 mg. Each dose strength will have a marking of SD 6, SD 9 and SD 12, corresponding to the dose strength and a distinct color: 6 mg - purple; 9 mg - blue; 12 mg - beige.

  • During dose adjustment, SD-809 ER will be supplied in weekly blister cards.
  • Once the investigator determines that a stable dose has been reached, SD-809 ER will be supplied in 30 count bottles.
Other Names:
  • SD-809
  • SD-809 Extended Release
Experimental: Rollover subjects
Rollover subjects are those who have successfully completed Study SD-809-C-15 and are continuing on long-term SD-809 ER after a 1-week wash out period.
Drug: SD-809 ER

SD-809 extended release (ER) tablets will be provided in dose strengths of 6, 9 and 12 mg. Each dose strength will have a marking of SD 6, SD 9 and SD 12, corresponding to the dose strength and a distinct color: 6 mg - purple; 9 mg - blue; 12 mg - beige.

  • During dose adjustment, SD-809 ER will be supplied in weekly blister cards.
  • Once the investigator determines that a stable dose has been reached, SD-809 ER will be supplied in 30 count bottles.
Other Names:
  • SD-809
  • SD-809 Extended Release

  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 a documented expanded CAG repeat (≥ 37) at or before Screening.
  3. Subject meets either of the following:

    • Has successfully completed participation in Study SD-809-C-15 OR
    • Has been receiving an FDA-approved dose of tetrabenazine that has been stable for ≥ 8 weeks before Screening and is providing a therapeutic benefit for control of chorea.
  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. Subject has provided a Research Advance Directive.
  8. 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 Baseline.
    • Stable hormonal contraception (with approved oral, transdermal, or depot regimen) for at least 3 months prior to screening.
  9. 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 Week 4, 8, 15, 28, 41 and 54 visits. Caregivers will be encouraged to attend other visits.
  10. Subject is able to ambulate without assistance for at least 20 yards (Note: The use of assistive devices (i.e., walker, cane) are permitted during ambulation).
  11. Has sufficient reading skills to comprehend the subject completed rating scales.

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 Baseline.
  5. Subject has an unstable or serious medical or psychiatric illness at Screening or Baseline.
  6. Subject has received tetrabenazine within 7 days of Baseline (Rollover subjects).
  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 (Rollover subjects only)

      • Switch subjects may receive Memantine if on a stable, approved dose for at least 30 days
  8. Subject has a score of ≥11 on the Swallowing Disturbance Questionnaire (SDQ) at Screening or Baseline.
  9. Subject has a Unified Parkinson's Disease Rating Scale (UPDRS) dysarthria score of ≥3 at Screening or Baseline.
  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 other than SD-809-C-15 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 or Baseline.
  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: NCT01897896

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Jenna Smith, RN, BSN    205-975-0338    jennat@uab.edu   
Contact: Victor Sung, MD, PhD    205-934-0683    vsung@uabmc.edu   
Principal Investigator: Victor Sung, MD, PhD         
United States, Arkansas
Washington Regional Medical Center Recruiting
Fayetteville, Arkansas, United States, 72703
Contact: Mary Craff, RN, CCRC    479-463-7856    mcraff@wregional.com   
Contact: Alan Diamond, MD    479-463-4444    adiamond@wregional.com   
Principal Investigator: Alan Diamond, MD         
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Brian Clemente, MA    310-794-1225    bclemente@mednet.ucla.edu   
Contact: Susan Perlman, MD    310-794-1195    sperlman@ucla.edu   
Principal Investigator: Susan Perlman, MD         
United States, Colorado
Rocky Mountain Movement Disorders Center Recruiting
Englewood, Colorado, United States, 80113
Contact: Breanna Nickels    303-357-5445    nickels@kumarneuro.com   
Contact: Christina Reeves, BS    303-357-5447    reeves@kumarneuro.com   
Principal Investigator: Rajeev Kumar, MD         
United States, Kansas
Hereditary Neurological Disease Centre (HNDC) Recruiting
Wichita, Kansas, United States, 67226
Contact: Greg Suter, BA    316-609-3020    hndcentre@aol.com   
Contact: William M Mallonee, MD    316-609-3020    hndcentre@aol.com   
Principal Investigator: William M Mallonee, MD         
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
Contact: Gregory Churchill    410-955-1349    gchurch3@jhu.edu   
Contact: Frederick Nucifora, DO, PhD    410-502-0518    nucifora@jhmi.edu   
Principal Investigator: Frederick Nucifora, DO, PhD         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Patricia Deppen, RN BSN MA    314-362-8548    deppenp@neuro.wustl.edu   
Contact: Susan Criswell, MD    314-362-7272    criswells@neuro.wustl.edu   
Principal Investigator: Susan Criswell, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Ronda Clouse, RN    212-305-2387    rc2682@cumc.columbia.edu   
Contact: Sarah Janicki, MD    212-342-1351    scj2110@mail.cumc.columbia.edu   
Principal Investigator: Sarah Janicki, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27705
Contact: Peggy Perry-Trice, CRC    919-684-0865    peggy.perrytrice@duke.edu   
Contact: Burton Scott, MD    919-668-2493    scott007@mc.duke.edu   
Principal Investigator: Burton Scott, MD         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Christine Hunter, RN, CCRC    713-798-3951    chunter@bcm.edu   
Contact: Joseph Jankovic, MD    713-798-7438    josephj@bcm.edu   
Principal Investigator: Joseph Jankovic, MD         
United States, Washington
Booth Gardner Parkinson's Care Center at Evergreen Hospital Medical Center Recruiting
Kirkland, Washington, United States, 98034
Contact: Julissa Leon, BS    425-899-5370    jaleon@evergreenhealth.com   
Contact: Pinky Agarwal, MD    425-899-3123    pagarwal@evergreenhealthcare.org   
Principal Investigator: Pinky Argarwal, MD         
Sponsors and Collaborators
Auspex Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Auspex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01897896     History of Changes
Other Study ID Numbers: SD-809-C-16
Study First Received: June 14, 2013
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Auspex Pharmaceuticals, Inc.:
Chorea
Huntington Disease

Additional relevant MeSH terms:
Chorea
Huntington Disease
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

ClinicalTrials.gov processed this record on April 17, 2014