CardiovascularShire Announces Study Results Of The Effects Of INTUNIV™ Extended Release On Secondary Measures In Children With ADHD And Oppositional Symptoms
Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced new findings on INTUNIV (guanfacine) extended release, a selective alpha-2A-agonist, at a major psychiatric meeting. This randomized placebo controlled trial met its primary objective, which was to evaluate the effects of INTUNIV on oppositional symptoms in children aged 6 to 12 years with a diagnosis of ADHD and the presence of oppositional symptoms. The data presented today on this investigational compound reviewed secondary efficacy measures from three different rating scales.
"A significant number of pediatric ADHD patients present with behaviors such as anger, resentfulness, defiance, and arguing with adults. It can be complicated for physicians and caregivers to find the right medication to control symptoms for children with ADHD exhibiting these behaviors," said Daniel Connor, MD, professor and division chief of child and adolescent psychiatry at the University of Connecticut Medical School. "When considered with the primary efficacy results of the current study, these data provide additional support for the clinical efficacy of INTUNIV for treating ADHD in this patient population."
On January 26, 2009, Shire filed a resubmission to the US Food and Drug Administration (FDA) of the New Drug Application to support approval for the treatment of ADHD in children and adolescents. Once available, INTUNIV will be the first selective alpha-2A receptor agonist approved for the treatment of ADHD.
INTUNIV Demonstrated Significant Efficacy in Secondary Endpoints
In this randomized, placebo-controlled, flexible-dose study, INTUNIV demonstrated significant ADHD symptom improvement in patients with oppositional symptoms as measured by the ADHD Rating Scale-IV (ADHD-RS-IV), a scale frequently used in ADHD clinical trials. In results from this study presented today, INTUNIV also demonstrated symptom improvement as measured by three different rating scales: the Clinical Global Impressions-Improvement (CGI-I), the Conduct Problem Subscale of the New York Parent Rating Scale-School-Aged (NYPRS-S), and the Parent Stress Index-Short Form (PSI/SF) questionnaire.
When using the CGI-I scale, investigators rated 7 out of 10 patients as "very much improved" or "much improved" compared with placebo (71.5 percent vs 32.0 percent; PAbout INTUNIV
INTUNIV is currently being studied as a once-daily, extended release formulation of guanfacine designed to provide steady delivery of drug throughout the day. INTUNIV is pending FDA approval for the treatment of ADHD in children and adolescents. In clinical trials, INTUNIV demonstrated significant reduction in ADHD symptoms. INTUNIV is not a controlled substance and has no known mechanism for abuse or dependence.
Guanfacine, the active ingredient in INTUNIV, is thought to work directly by binding selectively to alpha-2A adrenergic receptors located in the prefrontal cortex. The prefrontal cortex is an area of the brain associated with working memory, behavioral inhibition, regulation of attention, distractibility, and impulsivity. Although the mechanism of action of guanfacine in the treatment of ADHD is not fully understood, preclinical research suggests this selective alpha-2A agonist strengthens working memory and prefrontal cortex neuronal firing. This research supports the use of guanfacine for the treatment of ADHD.
In pivotal clinical trials, safety data showed that adverse events reported by participants using INTUNIV were generally mild to moderate in severity, with the most common side effects being sedative in nature. Sedation-related, treatment-emergent adverse events were among the most common and were usually transient and mild or moderate in severity. Treatment-related adverse events greater than 10 percent included somnolence (32 percent), headache (26 percent), fatigue (18 percent), upper abdominal pain (14 percent) and sedation (13 percent). Syncope occurred in approximately 1 percent of pediatric patients in the clinical program. The majority of these cases occurred in the long-term, open label studies. Small to modest changes in blood pressure, pulse rate, and ECG parameters were observed.
About ADHD
ADHD is one of the most common psychiatric disorders in children and adolescents. Worldwide prevalence of ADHD is estimated at 5.3 percent (with large variability), according to a comprehensive systematic review of this topic published in 2007 in the American Journal of Psychiatry. In the United States, approximately 7.8 percent of all school-aged children, or about 4.4 million US children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the Centers for Disease Control and Prevention (CDC).
ADHD is a psychiatric behavioral disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. The specific etiology of ADHD is unknown and there is no single diagnostic test for this syndrome. Adequate
diagnosis requires the use of medical and special psychological, educational and social res, utilizing diagnostic criteria such as Diagnostic and Statistical Manual of Mental Disorders™-IV (DSM-IV) or International Classification of Diseases 10 (ICD-10).
Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. Standard treatments include educational approaches, psychological, or behavioral modification, and medication.
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