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

Huntington's Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02507284
• Other study ID #: AVN011
• Secondary ID: 1U44NS090616-01A
• Status: Completed
• Phase: Phase 2
• Start date: May 10, 2016
• Est. completion date: December 21, 2018

Study information

• Verified date: July 2023
• Source: Azevan Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: December 21, 2018
• Est. primary completion date: September 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease
• Irritable Mood

Intervention

Drug:
• SRX246

• Placebo

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Hospital Translational Research Center	Aurora	Colorado
United States	University of Alabama	Birmingham	Alabama
United States	Massachusetts General Hospital	Charlestown	Massachusetts
United States	University of Virginia Health System, Department of Neurology	Charlottesville	Virginia
United States	Northwestern Out-Patient Neurology Clinic	Chicago	Illinois
United States	University Medical Arts Building	Cincinnati	Ohio
United States	Ohio State University, Wexner Medical Center, Department of Neurology	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	SUNY Stony Brook Clinical Research Center, Department of Neurology	East Setauket	New York
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	UCLA, Neurology Clinic	Los Angeles	California
United States	University of Miami, Miller School of Medicine, Jackson Behavioral Health Hospital	Miami	Florida
United States	Vanderbilt Clinical Research Center	Nashville	Tennessee
United States	Columbia University Medical Center, New York Presbyterian Hospital	New York	New York
United States	University of Pittsburgh Medical Center, Department of Neurology	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	UC Davis Medical Center, Department of Neurology, CTSC Clinical Research Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah, Department of Neurology	Salt Lake City	Utah
United States	Swedish Neuroscience Institute	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Azevan Pharmaceuticals	National Institute of Neurological Disorders and Stroke (NINDS), NeuroNEXT Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerability of SRX246	The primary endpoint, tolerability of SRX246, was assessed by the number of completers in each group.	12 weeks
Secondary	Safety of SRX246	The Safety of SRX246 was assessed by the number of participants who experience an adverse event.	12 weeks