Azevan Pharmaceuticals Inc — Department of Health and Human Services SBIR Phase I: 950

Description

DESCRIPTION provided by applicant Huntingtonandapos s Disease HD is an inherited disease that results from expansion of a trinucleotide CAG cytosine adenine guanine repeat that encodes a polyglutamine tract in the huntingtin protein Psychiatric symptoms including irritability and aggression are common in HD patients These are among the most distressing aspects of the disease They have adverse effects on daily life and often result in institutionalization Despite the frequent occurrence and severe consequences of irritability and aggression in HD these symptoms have received little attention to date Effective treatments are lacking and well validated scales for measuring changes in these symptoms are not available Faced with a significant unmet need neurologists cannot currently determine whether new drug therapies might be useful in treating neuropsychiatric symptoms in HD The Phase II clinical trial we propose in HD patients n andquot A randomized placebo controlled double blind multi center study to assess the tolerability of SRX in irritable aggressive subjects wit Huntingtonandapos s Disease HD andquot will allow us to rigorously evaluate the tolerability of a potential ne drug for the treatment of irritability and aggression It will also provide additional safety data n the compound and explore various rating scales for the assessment of changes in these symptoms Thus we will obtain critical data that can be used to plan future Phase II or III clinicl trials of drugs that might blunt irritability and aggression in HD The compound that we propose to test is SRX a first in class vasopressin a V a receptor antagonist SRX crosses the blood brain barrier following oral administration exhibits high affinity and selectivity for is target receptor has a strong safety profile is well tolerated in healthy volunteers and has excellent pharmacokinetics Extensive preclinical pharmacology studies and an experimental medicine fMRI study in healthy volunteers have shown that SRX has CNS effects after oral administration and that it modulates brain circuits involved in responses to stimuli that elicit aggression fear These findings strongly suggest that SRX might have a beneficial effect on the irritability and aggression seen in a sizable proportion of HD patients The proposed project will generate data needed to plan a future clinical trial that can rigorously test SRX for efficacy as a treatment for irritability and aggression PUBLIC HEALTH RELEVANCE In Huntingtonandapos s Disease HD psychiatric symptoms including irritability and aggression adversely impact daily life and often result in institutionalization New medicines to treat these neuropsychiatric symptoms are needed because available drugs are minimally effective and several have significant side effects In the proposed clinical trial SRX a novel first in class vasopressin a V a receptor antagonist that shows promise as a treatment for irritability and aggression will be tested in HD patients to assess tolerability generate additional safety data and explore scales that measure these symptoms for use in future clinical trials