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Tolerability, Safety, and Activity of SRX246 in Irritable Subjects With Huntington's Disease

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ClinicalTrials.gov Identifier: NCT02507284
Recruitment Status : Completed
First Posted : July 23, 2015
Last Update Posted : October 23, 2019
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
NeuroNEXT Network
Information provided by (Responsible Party):
Azevan Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE July 22, 2015
First Posted Date  ICMJE July 23, 2015
Last Update Posted Date October 23, 2019
Actual Study Start Date  ICMJE May 10, 2016
Actual Primary Completion Date September 10, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2019)
Tolerability, defined as the proportion of completers. [ Time Frame: 12 weeks ]
Assess the proportion of completers.
Original Primary Outcome Measures  ICMJE
 (submitted: July 22, 2015)
Tolerability: Assess the proportion of completers [ Time Frame: 12 weeks ]
Assess the proportion of completers.
Change History Complete list of historical versions of study NCT02507284 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2019)
Safety, defined as the proportion of participants who experience an adverse event. [ Time Frame: 12 weeks ]
Assess the proportion of participants who experience an adverse event.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2015)
Safety: Assess the proportion of participants who experience an adverse event [ Time Frame: 12 weeks ]
Assess the proportion of participants who experience an adverse event.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 22, 2015)
Activity: Examine several measures of irritability and other problem behaviors, and clinical assessments for activity signal. [ Time Frame: 12 weeks ]
Examine several measures of irritability and other problem behaviors, and clinical assessments for activity signal.
 
Descriptive Information
Brief Title  ICMJE Tolerability, Safety, and Activity of SRX246 in Irritable Subjects With Huntington's Disease
Official Title  ICMJE An Exploratory Phase II Study to Determine the Tolerability, Safety, and Activity of a Novel Vasopressin 1a Receptor Antagonist (SRX246) in Irritable Subjects With Huntington's Disease (HD)
Brief Summary This study evaluates the tolerability, safety and activity of SRX246 in the treatment of irritability in patients with Huntington's disease. Two-thirds of all participants will receive SRX246, while the other third will receive a placebo.
Detailed Description

SRX246 is a first-in-class vasopressin 1a (V1a) receptor antagonist that crosses the blood-brain barrier following oral administration. The molecule exhibits high affinity and high selectivity for its target receptor. Preclinical pharmacology studies have demonstrated significant CNS effects in models of irritability, including impulsive aggression, depression, and anxiety. In an experimental medicine fMRI study in healthy volunteers, SRX246 treatment significantly attenuated the effect of intranasal AVP in brain circuits known to modulate emotional responses to stimuli that elicit aggression/fear. Together, these findings suggest that SRX246 has potential as a novel therapeutic agent for major neuropsychiatric symptoms seen in HD patients.

This is a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12 week, dose escalation study of SRX246 in irritable Subjects with early symptomatic HD.

Following an initial screening visit, Subjects fulfilling the study inclusion and exclusion criteria will enter a pre-treatment screening phase to permit evaluations to confirm eligibility for inclusion into the study. This screening phase will be no longer than 30 days. At the completion of the screening period, eligible Subjects will be randomized at baseline visit to receive either placebo or final doses of SRX246 of 120 mg twice daily or 160 mg twice daily during the double-blind treatment phase. At baseline, Subjects in the active groups will receive 80 mg twice daily for 2 weeks, then escalate to 120 mg twice daily for 4 weeks. Then one group of Subjects will continue to take 120 mg of SRX246 twice daily for an additional 6 weeks, and the second group of Subjects will increase their dose to 160 mg of SRX246 twice daily for 6 weeks. Total dosing duration is 12 weeks.

Subjects in the placebo group will receive a similar number of capsules that are identical in appearance to the capsules that contain SRX246 during the trial, in order to preserve the blind.

In all groups, dose escalation will occur (stepwise) if patients have not experienced dose-limiting adverse effects. Patients who cannot tolerate their final dose of drug (or placebo) can have this dose reduced without compromising the blinding.

Subjects will have periodic visits either "in-person" or by "telephone", to assess tolerability, safety, and several measures of irritability and other problem behaviors, and clinical assessments for activity signals.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Irritable Mood
  • Huntington's Disease
Intervention  ICMJE
  • Drug: SRX246
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: SRX246 120mg BID
    SRX246 capsules, administered orally, in divided doses twice daily
    Intervention: Drug: SRX246
  • Experimental: SRX246 160mg BID
    SRX246 capsules, administered orally, in divided doses twice daily
    Intervention: Drug: SRX246
  • Placebo Comparator: Placebo
    Placebo capsules, administered orally, in divided doses twice daily
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 16, 2018)
106
Original Estimated Enrollment  ICMJE
 (submitted: July 22, 2015)
108
Actual Study Completion Date  ICMJE December 21, 2018
Actual Primary Completion Date September 10, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  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. 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.
  7. 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.
  8. Subjects must be able to swallow study drug capsules whole.
  9. Sufficient English skills to complete all assessments without assistance of an English language interpreter. Subjects with HD who cannot read or write might qualify for enrollment in the study. Site PIs will have to decide in each case whether the Subject can understand and fully participate with help from his/her Informant.
  10. Availability of a responsible Informant (referred to as a "study partner" in the consent document) 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 patient attends all study visits and takes the study medicine as instructed. The study partner must spend time with the patient a minimum of 4 times per week on 4 separate days, and must monitor the patient's compliance and adverse events, participate in caregiver assessments, and use the eDiary.
  11. 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.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02507284
Other Study ID Numbers  ICMJE AVN011
1U44NS090616-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Azevan Pharmaceuticals
Study Sponsor  ICMJE Azevan Pharmaceuticals
Collaborators  ICMJE
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • NeuroNEXT Network
Investigators  ICMJE Not Provided
PRS Account Azevan Pharmaceuticals
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP