Phase II Data Demonstrate Abbott's Most Advanced NNR Candidate ABT-089
Shows Strong Safety, Tolerability And Efficacy in Adults With ADHD
ABBOTT PARK, Ill., May 7 /PRNewswire-FirstCall/ -- Abbott (NYSE: ABT) and other leading scientists will present new Phase II data showing that ABT-089, a selective neuronal nicotinic receptor (NNR) agonist, is a potentially effective and safe treatment for adults with Attention-Deficit Hyperactivity Disorder (ADHD). The studies are being presented today at the American Psychiatric Association (http://www.psych.org/) 161st Annual Meeting in Washington, D.C.
Phase II study results show that ABT-089 appears to significantly improve the core symptoms of ADHD, improve quality-of-life and work effectiveness, and reduce overall work impairment in adults with ADHD. Data also revealed that ABT-089 appears to be generally well tolerated with no significant negative effects on sleep, appetite or vital signs (heart rate and blood pressure).
ADHD, an ailment historically associated with childhood, persists into adulthood in more than two-thirds of cases. While medical treatment can improve the symptoms of ADHD, currently approved treatments often cause undesirable side effects, including increases in heart rate and blood pressure.
ABT-089 appears to exhibit an improved profile compared to current treatments by improving the core and associated symptoms of ADHD without clinically significant side effects. The compound targets specific types of NNRs found on nerve cells in the central nervous system. NNRs, also known as neuronal nicotinic acetylcholine receptors (nAChRs), modulate the release of several important neurotransmitters, such as acetylcholine and dopamine, and are an important class of ion channels (molecular "gates" that control the flow of ions in and out of cells and regulate neuron signaling) that have been associated with a number of neurological conditions.
"We have seen therapeutic promise in targeting NNRs for more than a decade, for both pain and the cognitive deficits associated with a variety of diseases, including ADHD and Alzheimer's disease," said James Sullivan, Ph.D., divisional vice president, Neuroscience Discovery, Abbott. "We are very encouraged with the results of our ADHD work; this is a condition that demands innovative treatments, particularly to address side effect issues that have been observed with current treatments."
"The studies evaluating efficacy demonstrated that ABT-089 reduced the severity of symptoms and was generally well tolerated in adults with ADHD," said Timothy Wilens, M.D., associate professor of psychiatry, director of Substance Abuse Services in Pediatric Psychopharmacology at Massachusetts General Hospital. "Not all NNR agonists may be suitable for the treatment of ADHD. By selectively targeting specific NNR receptors, ABT-089 appears to have a favorable profile for treating the condition."
Study Background and Results
Two-hundred-twenty-one adults with ADHD enrolled in the multicenter, randomized, double-blind, placebo-controlled study, which used a 2 x 2 crossover design. Each subject received both placebo (PBO) and active treatment in random sequence. Five doses of ABT-089 were evaluated: 2 mg, 5 mg, 15 mg, or 40 mg once daily (QD), or 40 mg twice daily (BID). Each treatment period was 4 weeks, separated by a 2-week washout period. The endpoint was the Investigator-rated Conners' Adult ADHD Rating Scale (CAARS- Inv) Total Score obtained at the end of each treatment period.
Results showed ABT-089 at doses of 40mg QD and 40 mg BID were generally well tolerated, did not negatively impact heart rate or blood pressure and were significantly more effective than placebo in the treatment of adults with ADHD. ABT-089 also demonstrated efficacy on secondary endpoints such as the Adult ADHD Investigator Symptom Report Scale (AISRS) and the self-reported ratings on the Conners' Adult ADHD Rating Scale (CAARS-self).
Moreover, data measured by the Adult ADHD Quality of Live (AAQoL) instrument and the Work Productivity and Activity Impairment (WPAI) scale demonstrated that treatment with ABT-089 appears to significantly improve quality of life and work effectiveness. Using the WPAI scale, subjects reported improvements in work productivity (17 percent) and work effectiveness (14.2 percent), as well as a reduction in absenteeism (6.7 percent).
The most common adverse events observed were headache, insomnia and
upper respiratory infection.
Abbott presentations during APA Annual Meeting
New Research Poster Sessions 6, May 7, noon - 2pm ET
* Efficacy and Safety of ABT-089 in Adults with ADHD
* Patient Reported Overall Clinical Improvement Associated with ABT-089 in
* Clinical Validity of Adult ADHD Quality of Life (AAQoL) Scale Evaluated
in an Adult ADHD Clinical Trial
* Quality of Life and Work Productivity Improvements Associated with
ABT-089 in Adults with ADHD
* Effects of ABT-089 on Heart Rate and Blood Pressure in Adults
Abbott Neuroscience Portfolio
Building on the company's strong scientific foundation in neuroscience and pain, Abbott has significant research and development efforts underway to investigate new therapeutic approaches to cognitive disorders, such as ADHD, Alzheimer's disease and schizophrenia. Abbott also is investigating new therapies for nociceptive pain conditions such as osteoarthritis and cancer pain, as well as neuropathic pain conditions such as diabetic neuropathy. Abbott scientists have been among the leaders in advancing the understanding of the therapeutic potential of NNRs for more than a decade and have published more than 75 research studies in this area.
alpha 4 beta 2 NNR Agonist Program
ABT-089 is a selective NNR agonist, which targets the alpha 4 beta 2 NNR subtype. It has demonstrated efficacy in preclinical models of attention, learning and memory deficits. It also has demonstrated efficacy in improving the core symptoms of attention-deficit hyperactivity disorder in adults. ABT- 089 is currently in Phase II clinical trials for ADHD and Alzheimer's disease.
ABT-894 is an NNR agonist, which targets the alpha 4 beta 2 NNR subtype. It has demonstrated efficacy in multiple preclinical animal models of neuropathic pain and nociceptive pain with and without an inflammatory component. ABT-894 exhibits high affinity for and full functional efficacy at the alpha 4 beta 2 NNR subtype. Similar to other NNR agonists, it also has demonstrated a cognitive enhancing profile in pre-clinical models of cognition. ABT-894 is currently in Phase II clinical trials for ADHD and diabetic neuropathic pain. This compound was discovered in collaboration with NeuroSearch.
alpha 7 NNR Agonist Program
ABT-107 is a potent and selective NNR agonist, which targets the alpha 7 NNR subtype. It has demonstrated efficacy in in vivo studies that model memory consolidation, social recognition memory, working memory, and sensory gating deficits, which are domains of cognition negatively impacted in Alzheimer's disease and schizophrenia. ABT-107 is currently in Phase I clinical trials for a variety of central nervous system disorders. This compound was discovered in collaboration with NeuroSearch.
TRPV1 Receptor Program
The TRPV1, or vanilloid receptor, plays an important role in mediating the body's response to a variety of pain stimuli, including heat and changes in pH levels, as well as a variety of mediators of inflammation that are released in the body following tissue damage. Abbott has identified a number of compounds that may have the ability to elicit relief across a broad spectrum of pain states. The lead compounds have demonstrated efficacy comparable to morphine across a number of different pre-clinical pain models -- including osteoarthritis, post-operative and cancer pain.
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 68,000 people and markets its products in more than 130 countries.
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