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

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2016 by Azevan Pharmaceuticals
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
NeuroNEXT Network
Information provided by (Responsible Party):
Azevan Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02507284
First received: July 22, 2015
Last updated: June 21, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Irritable Mood Huntington's Disease Drug: SRX246 Drug: Placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Azevan Pharmaceuticals:

Primary Outcome Measures:
  • Tolerability: Assess the proportion of completers [ Time Frame: 12 weeks ]
    Assess the proportion of completers.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 108
Study Start Date: June 2016
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SRX246 120mg BID
SRX246 capsules, administered orally, in divided doses twice daily
Drug: SRX246
Experimental: SRX246 160mg BID
SRX246 capsules, administered orally, in divided doses twice daily
Drug: SRX246
Placebo Comparator: Placebo
Placebo capsules, administered orally, in divided doses twice daily
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02507284

Contacts
Contact: Neal G Simon, PhD 610-419-1057 ngsimon@azevan.com

  Show 22 Study Locations
Sponsors and Collaborators
Azevan Pharmaceuticals
National Institute of Neurological Disorders and Stroke (NINDS)
NeuroNEXT Network
  More Information

Responsible Party: Azevan Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02507284     History of Changes
Other Study ID Numbers: AVN011
1U44NS090616-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: July 22, 2015
Last Updated: June 21, 2016

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
SRX246
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 26, 2017