AZD3480 and AZD1446 are novel small molecules that act selectively on the alpha4beta2 NNR subtype. We have granted to AstraZeneca an exclusive license for the worldwide development and commercialization of AZD3480 and AZD1446 for various conditions characterized by cognitive impairment under a 2005 collaborative research and license agreement.
We or AstraZeneca have studied AZD3480 in six Phase 2 clinical trials in disorders marked by varying types and degrees of cognitive impairment, including attention deficit/hyperactivity disorder (ADHD), Alzheimer’s disease, mild cognitive impairment (MCI), age associated memory impairment (AAMI) and cognitive dysfunction in schizophrenia (CDS). As of October 2010, AZD3480 has been evaluated in approximately 1,350 subjects.
AZD3480 is under consideration for potential further development in ADHD. In a Phase 2 clinical trial in adults with ADHD that we completed in 2009, AZD3480 met the primary outcome measure, total symptom score on the Conners’ Adult ADHD Rating Scale – Investigator Rating (CAARS-INV). In the study, adult subjects received in random order daily doses of 5mg of AZD3480, 50mg of AZD3480 and placebo, each for two weeks with the dosing periods separated by a three-week washout period. At 50mg AZD3480, subjects showed statistically significant (p < .01) improvement in symptoms of ADHD as measured by CAARS-INV.
AstraZeneca is currently assessing AZD3480 in non-clinical studies to determine if the therapeutic index will support further development across the broad ADHD population. If AstraZeneca determines that AZD3480 is suitable for advancement, we expect the next trial would be a Phase 2b clinical trial in adults with ADHD.
Additional information regarding AZD3480 clinical trials is available at http://www.clinicaltrials.gov/ct2/results?term=azd3480.
About ADHD
Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders. The principal characteristics of ADHD are inattention, hyperactivity and impulsivity. ADHD is a chronic disorder that develops during childhood, often persists into adulthood and can negatively impair many aspects of daily life, including home, school, work and interpersonal relationships. The market research firm Business Insights estimated that there were approximately 23.3 million adults and 21.6 million children and adolescents with ADHD in 2009 in the world's seven major pharmaceutical markets (United States, France, Germany, Italy, Spain, United Kingdom and Japan).
Current medications approved to treat ADHD include stimulants (e.g., amphetamine, methylphenidate) and the non-stimulant atomoxetine, all of which are scheduled. In addition to the burdens associated with scheduled drugs, these medications have a variety of side effects, including insomnia, increased heart rate, blood pressure and loss of appetite and behavioral changes such as irritability. A well tolerated, non-stimulant treatment for ADHD that is not scheduled would represent a significant advance for patients.