NN105: Tolerability, Safety and Activity of SRX246 in Irritable Subjects with HD

Principal Investigator: Gordon Smith
Keywords: Huntington's Disease , Irritability Department: Neurology
IRB Number: 00088612 Co Investigator:  
Specialty: Neurology, Neurology, Neurology, Neurology, Neurology
Sub Specialties: Neurogenetics, Movement Disorders, Chorea, Huntington Disease, Neurodegenerative Disorders
Recruitment Status: Not yet recruiting

Contact Information

Paola Wall
paola.wall@hsc.utah.edu
801-581-4543

Brief Summary

Primary Objective: tolerability

To assess the tolerability of SRX246 in irritable Subjects with early symptomatic HD over a period of 12 weeks compared to placebo.

Secondary Objective:safety

To assess the safety of SRX246 in irritable Subjects with early symptomatic HD over a period of 12 weeks compared to placebo.

Exploratory Objectives:

To explore the activity of SRX246 in irritable Subjects with early symptomatic HD over a period of 12 weeks compared to placebo, using measures of irritability and other problem behaviors:  Aberrant Behavior Checklist (ABC), Cohen-Mansfield Agitation Inventory (CMAI), Problem Behaviors Assessment - short form (PBA-s), and Irritability Scale (IS). 

To explore the use of Clinical Global Impression (CGI), Quality of Life (QoL) and Caregiver Burden questionnaires in irritable Subjects with early symptomatic HD who are given SRX246 over a period of 12 weeks compared to placebo.  

To explore the use of an eDiary to prompt Subjects to take study drug, and to assess mood and behavior.

To collect sparse sampling population pharmacokinetic data for SRX246 administered to irritable Subjects with early symptomatic HD.

Inclusion Criteria

Inclusion Criteria

  1. Male and female Subjects aged 18 years or older.

  2. Subjects must have clinical features of HD, which can include motor, cognitive, or behavioral symptoms.

  3. A confirmatory family history of HD; OR CAG repeat expansion 37.

  4. Total Functional Capacity (TFC) score of 5-13.

    1. If TFC<7 administer MoCA. If MoCA score less than 20, surrogate consent required.

  5. Evidence of irritability; a score of at least 2 or greater on the severity measure of either the UHDRS Irritability question (30b) or Aggression question (Disruptive or Aggressive Behavior, 31b).

  6. Medications prescribed for mood, behavior, or neurologic symptoms must be stable for 30 days prior to the Baseline Visit.

  7. Women of childbearing potential (i.e., those not postmenopausal or surgically sterile) must have a negative pregnancy test, be non-lactating and use adequate contraception methods during the study. Adequate birth control includes: abstinence; oral, implanted or injected contraceptives, e.g., birth control pills; intra-uterine device; barrier (vaginal ring or diaphragm/cervical cap with spermicide); transdermal patch.Reliable contraception must have been in use 30 days prior to the Baseline Visit.Partner(s) contraception (e.g., male partner with vasectomy or other surgical contraception) is acceptable.

  8. Men must agree not to father a child during the study and one month after and to use contraception. Barrier with spermicide or surgical contraception is acceptable.Partner(s) contraception (e.g., female partner taking birth control pills or surgically sterile) is acceptable.

  9. Subjects must be able to swallow study drug capsules whole.

  10. Sufficient English skills to complete all assessments without assistance of an English language interpreter.

  11. Availability of a responsible Study Partner who has good English skills, is familiar with the Subject, and is able and willing to comply with all required study procedures, ensuring that the Subject attends all study visits and takes the study medicine as instructed.The Study Partner must spend time with the Subject a minimum of 4 times per week on 4 separate days, and must monitor the Subject's compliance and adverse events, participate in Study Partner assessments, and use the eDiary.

  12. Subject has provided written, informed consent or, if Subject lacks the capacity to provide informed consent, a legally authorized representative (LAR) has

Exclusion Criteria

Exclusion Criteria

  1. Any significant neurologic disease other than HD at Screening.

  2. Severe psychotic features or other severe psychiatric symptoms within the last three months which could lead to difficulty complying with the protocol.

  3. History of active alcohol or substance abuse within the past two years or Subject is unable to refrain from substance abuse throughout the study.

  4. Any chronic disability, significant systemic illness or unstable medical condition at Screening or Baseline that could lead to difficulty complying with the protocol.

  5. Use of any investigational drugs within 30 days of Screening.

  6. Subject has known allergy to any of the components of study medication.

  7. Subject is currently pregnant, breast-feeding and/or lactating.

  8. Subject acknowledges present use of illicit drugs at Screening.

  9. Active suicidal ideation in the judgement of the Investigator