 |
|
Shire announces once-daily guanfacine extended release data in ADHD patients aged 6 to 17 years
November 20, 2006Shire plc (Nasdaq: SHPGY, LSE: SHP, TSX: SHQ) announced today that once-daily doses of the investigational medication guanfacine extended release (GXR, also referred to as SPD503), a selective alpha-2A-adrenoceptor agonist, significantly improved symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in children aged 6 to 17 years when used as a monotherapy. The phase III trial results were presented today at the 2006 U.S. Psychiatric & Mental Health Congress (USPMHC) annual meeting. Two additional studies also released at the meeting report the pharmacokinetic profile of guanfacine extended release.
Shire submitted a New Drug Application (NDA) for guanfacine extended release on August 24, 2006. If approved, guanfacine extended release, which is not a central nervous system stimulant, will be the first once-daily selective alpha-2A-adrenoceptor agonist compound indicated for the treatment of ADHD.
"Guanfacine extended release was developed to allow once-daily dosing through a controlled release formulation," said Eliseo Salinas, MD, Shire EVP and Chief Scientific Officer. "Research studies have shown that the extended-release formulation of guanfacine effectively provided day-long ADHD symptom control with a single daily dose based on several standard symptom measures."
Monotherapy with Once-Daily Guanfacine Extended Release Significantly Improved ADHD Symptoms In this study, investigators randomized 345 subjects to receive placebo or 2 mg, 3 mg or 4 mg guanfacine extended release once daily. The study consisted of three periods: screening (maximum of 14 days), washout (about one week for discontinuation of current ADHD medication) and double-blind treatment (eight weeks). Titration was done in a forced-dose manner by increasing guanfacine extended release in 1 mg increments per week, from 1 mg per day during the first week to a maximum of 4 mg daily in weeks four and five according to randomization. The guanfacine extended release dose was then decreased at the same weekly rate starting in weeks six and seven.
Compared to placebo, children aged 6 to 17 years treated with guanfacine extended release showed significant improvements in the core symptoms of ADHD (hyperactivity, impulsivity and inattention), as reflected by total scores on the primary efficacy measurement, the ADHD Rating Scale (ADHD-RS-IV). The ADHD-RS-IV is a standard test for diagnosing ADHD in children and adolescents and for assessing their response to treatment. The scale, which contains 18 items, is based on the ADHD diagnosis criteria as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision?, a publication of the American Psychiatric Association. A reduction in the ADHD-RS-IV score reflects improvement.
Overall, average reductions in ADHD-RS-IV total scores were 16.7 points for guanfacine extended release and 8.9 for placebo (P <.0001). Investigators observed improvement in ADHD-RS-IV scores as early as two weeks after dosing began, with significant improvement in all guanfacine extended release dose groups occurring at the third week and continuing through the last evaluation at week five. Also, an analysis by weight-adjusted actual dose (mg/kg) showed reductions in ADHD-RS-IV total scores from baseline of 34 percent to 65 percent for guanfacine extended release doses compared with 23 percent for placebo.
Significance was also seen in all secondary efficacy measures, which included scores on the Clinical Global Impression of Improvement (CGI-I), Clinical Global Impression of Severity (CGI-S), Conners' Parent Rating Scale- Revised: Short Form (CPRSR) and Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R).
"As the first selective alpha-2A-adrenoceptor agonist being developed as an ADHD treatment, guanfacine extended release will be a welcomed addition to our armamentarium of ADHD medications. In this clinical trial, guanfacine extended release significantly improved ADHD symptoms based on several standard measures of response," noted Raun Melmed, MD, Medical Director of the Melmed Center in Scottsdale, AZ. "As a practicing physician I can say our community is always interested in expanding the range of ADHD treatment options which need to be used in the context of an overall treatment program, so patients can receive individualized and optimal care."
Guanfacine extended release was generally well-tolerated in this study. The most commonly reported treatment-emergent adverse events were somnolence, headache, fatigue, upper abdominal pain, and sedation. Incidence of sedative events (somnolence, sedation and fatigue) were usually mild or moderate in severity. Modest decreases in mean systolic and diastolic blood pressure and pulse were reported.
Guanfacine Extended Release Formulation and Pharmacokinetics Data Guanfacine extended release, a novel formulation of guanfacine, was developed by incorporating ionic polymers, enteric polymers, and organic acids within the tablet matrix. This formulation was designed to control and prolong the release of guanfacine, in contrast to the immediate, burst-like release provided by the commercially available Immediate Release (IR) formulation of guanfacine, which is indicated as a treatment for hypertension.
In a single-dose, pharmacokinetic study with healthy adults, guanfacine extended release had a doubling of Tmax and a significant reduction in Cmax versus immediate release guanfacine.
Shire Development Inc. supported the three guanfacine extended release studies.
About Guanfacine Extended Release Shire is seeking approval of 1 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg and 4 mg once-daily guanfacine extended release doses for the control of ADHD symptoms throughout the day in children aged 6 to 17 years. The guanfacine extended release NDA includes data from two placebo-controlled trials in children and adolescents ages 6 to 17 evaluating the compound's safety and efficacy in controlling ADHD symptoms evaluated on a once-weekly basis using the ADHD Rating Scale, which included both hyperactive/impulsive and inattentive subscales.
Guanfacine extended release is a once-daily formulation of the selective alpha-2A-adrenoceptor agonist. Unlike some other ADHD treatments, guanfacine extended release is not a central nervous system stimulant or a controlled substance.
Adrenergic receptors are present on almost all kinds of cells in the body and act as receptors for two neurotransmitters, epinephrine (adrenaline) and norepinephrine, used by nerve cells to communicate. An agonist is a molecule that acts similar to these neurotransmitters by also binding to receptors. It is hypothesized that guanfacine HCl binds to the alpha-2A-adrenergic cell receptor to act directly in the part of the brain called the prefrontal cortex, an area that is associated with working memory, behavioral inhibition, attention and cognitive control, as well as the ability to orchestrate thought and action.
About ADHD Approximately 7.8 percent of all school-age children, or about 4.4 million U.S. children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the U.S. Centers for Disease Control and Prevention (CDC). ADHD is one of the most common psychiatric disorders in children and adolescents. ADHD is a neurobiological psychiatric 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. To be properly diagnosed with ADHD, a child needs to demonstrate at least six of nine symptoms of inattention; at least six of nine symptoms of hyperactivity/impulsivity; the onset of such symptoms before age 7 years; that some impairment from the symptoms is present in two or more settings (e.g., at school and home); that the symptoms continue for at least six months; and that there is clinically significant impairment in social, academic or occupational functioning.
Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioral modification, and medication.
Porter Novelli
Monotherapy with Once-Daily Guanfacine Extended Release Significantly Improved ADHD Symptoms In this study, investigators randomized 345 subjects to receive placebo or 2 mg, 3 mg or 4 mg guanfacine extended release once daily. The study consisted of three periods: screening (maximum of 14 days), washout (about one week for discontinuation of current ADHD medication) and double-blind treatment (eight weeks). Titration was done in a forced-dose manner by increasing guanfacine extended release in 1 mg increments per week, from 1 mg per day during the first week to a maximum of 4 mg daily in weeks four and five according to randomization. The guanfacine extended release dose was then decreased at the same weekly rate starting in weeks six and seven.
Compared to placebo, children aged 6 to 17 years treated with guanfacine extended release showed significant improvements in the core symptoms of ADHD (hyperactivity, impulsivity and inattention), as reflected by total scores on the primary efficacy measurement, the ADHD Rating Scale (ADHD-RS-IV). The ADHD-RS-IV is a standard test for diagnosing ADHD in children and adolescents and for assessing their response to treatment. The scale, which contains 18 items, is based on the ADHD diagnosis criteria as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision?, a publication of the American Psychiatric Association. A reduction in the ADHD-RS-IV score reflects improvement.
Overall, average reductions in ADHD-RS-IV total scores were 16.7 points for guanfacine extended release and 8.9 for placebo (P <.0001). Investigators observed improvement in ADHD-RS-IV scores as early as two weeks after dosing began, with significant improvement in all guanfacine extended release dose groups occurring at the third week and continuing through the last evaluation at week five. Also, an analysis by weight-adjusted actual dose (mg/kg) showed reductions in ADHD-RS-IV total scores from baseline of 34 percent to 65 percent for guanfacine extended release doses compared with 23 percent for placebo.
Significance was also seen in all secondary efficacy measures, which included scores on the Clinical Global Impression of Improvement (CGI-I), Clinical Global Impression of Severity (CGI-S), Conners' Parent Rating Scale- Revised: Short Form (CPRSR) and Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R).
"As the first selective alpha-2A-adrenoceptor agonist being developed as an ADHD treatment, guanfacine extended release will be a welcomed addition to our armamentarium of ADHD medications. In this clinical trial, guanfacine extended release significantly improved ADHD symptoms based on several standard measures of response," noted Raun Melmed, MD, Medical Director of the Melmed Center in Scottsdale, AZ. "As a practicing physician I can say our community is always interested in expanding the range of ADHD treatment options which need to be used in the context of an overall treatment program, so patients can receive individualized and optimal care."
Guanfacine extended release was generally well-tolerated in this study. The most commonly reported treatment-emergent adverse events were somnolence, headache, fatigue, upper abdominal pain, and sedation. Incidence of sedative events (somnolence, sedation and fatigue) were usually mild or moderate in severity. Modest decreases in mean systolic and diastolic blood pressure and pulse were reported.
Guanfacine Extended Release Formulation and Pharmacokinetics Data Guanfacine extended release, a novel formulation of guanfacine, was developed by incorporating ionic polymers, enteric polymers, and organic acids within the tablet matrix. This formulation was designed to control and prolong the release of guanfacine, in contrast to the immediate, burst-like release provided by the commercially available Immediate Release (IR) formulation of guanfacine, which is indicated as a treatment for hypertension.
In a single-dose, pharmacokinetic study with healthy adults, guanfacine extended release had a doubling of Tmax and a significant reduction in Cmax versus immediate release guanfacine.
Shire Development Inc. supported the three guanfacine extended release studies.
About Guanfacine Extended Release Shire is seeking approval of 1 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg and 4 mg once-daily guanfacine extended release doses for the control of ADHD symptoms throughout the day in children aged 6 to 17 years. The guanfacine extended release NDA includes data from two placebo-controlled trials in children and adolescents ages 6 to 17 evaluating the compound's safety and efficacy in controlling ADHD symptoms evaluated on a once-weekly basis using the ADHD Rating Scale, which included both hyperactive/impulsive and inattentive subscales.
Guanfacine extended release is a once-daily formulation of the selective alpha-2A-adrenoceptor agonist. Unlike some other ADHD treatments, guanfacine extended release is not a central nervous system stimulant or a controlled substance.
Adrenergic receptors are present on almost all kinds of cells in the body and act as receptors for two neurotransmitters, epinephrine (adrenaline) and norepinephrine, used by nerve cells to communicate. An agonist is a molecule that acts similar to these neurotransmitters by also binding to receptors. It is hypothesized that guanfacine HCl binds to the alpha-2A-adrenergic cell receptor to act directly in the part of the brain called the prefrontal cortex, an area that is associated with working memory, behavioral inhibition, attention and cognitive control, as well as the ability to orchestrate thought and action.
About ADHD Approximately 7.8 percent of all school-age children, or about 4.4 million U.S. children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the U.S. Centers for Disease Control and Prevention (CDC). ADHD is one of the most common psychiatric disorders in children and adolescents. ADHD is a neurobiological psychiatric 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. To be properly diagnosed with ADHD, a child needs to demonstrate at least six of nine symptoms of inattention; at least six of nine symptoms of hyperactivity/impulsivity; the onset of such symptoms before age 7 years; that some impairment from the symptoms is present in two or more settings (e.g., at school and home); that the symptoms continue for at least six months; and that there is clinically significant impairment in social, academic or occupational functioning.
Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioral modification, and medication.
Porter Novelli
Adhd News and Current Adhd Events RSSBarrow scientists work their magic
Two neuroscientists at Barrow Neurological Institute at St. Joseph's Hospital and Medical Center are turning magic tricks into science.
APA task force recommends dissemination of evidence-based practice
An estimated 15 million American children are diagnosed with a mental disorder, but only about a quarter of them are getting appropriate treatment based on scientific evidence.
Innovative program focuses on improved care for children with ADHD
An innovative program is helping busy primary care physicians improve the care they provide for school-aged children with Attention-Deficit/Hyperactivity Disorder (ADHD), according to a study led by researchers at Cincinnati Children's Hospital Medical Center and published in the July edition of Pediatrics.
Did the gene for ADHD help our nomadic ancestors?
An ADHD-associated version of the human gene DRD4 is linked to better health among nomadic tribesmen, but may cause malnourishment in their settled cousins, according to new research by a team directed by an anthropologist at the University of Wisconsin-Milwaukee (UWM).
PET imaging focuses on medication's purported ability to improve mental performance
Concerned by the growing numbers of people using stimulant medications such as methylphenidate (MP)-either legally or illegally-to improve attention and focus, researchers used positron emission tomography (PET) imaging with the radiotracer fluorodeoxyglucose (FDG) to assess the effects of the drug on brain function in the normal human brain.
Knowing looks: Using gaze aversion to tell when children are learning
People use eye contact in a variety of ways every minute of every day but how often do you find yourself staring into space with concentrating on an issue or problem? Psychologists now know that people who are carrying out a complex task tend to look away from anyone else who is nearby. They refer to it as 'gaze aversion'.
Report confirms increased risk of smoking, substance abuse in bipolar adolescents
A study from the Massachusetts General Hospital (MGH) supports previous reports that adolescents with bipolar disorder are at increased risk for smoking and substance abuse.
Children's diet not the main cause of ADHD
Food may not be the major cause of hyperactivity in children. Genetics, brain function and parental actions such as smoking may be just as important.
A trial of removing food additives should be considered for hyperactive children
A properly supervised trial eliminating colours and preservatives from the diet of hyperactive children should considered a part of the standard treatment, says an editorial in this week's BMJ.
Phase III pivotal results presented of VYVANSE to treat ADHD in adults
Shire plc (LSE: SHP, Nasdaq: SHPGY), the global specialty biopharmaceutical company, today presented the results of a phase III pivotal study in which VYVANSE demonstrated significant improvements in Attention Deficit Hyperactivity Disorder (ADHD) symptoms in adults and met all safety and efficacy endpoints.
More Adhd News Articles
 | Change Your Brain, Change Your Life: The Breakthrough Program for Conquering Anxiety, Depression, Obsessiveness, Anger, and Impulsiveness by Daniel G. Amen In this age of do-it-yourself health care (heck, if the doctor only sees you for 10 minutes each visit, what other options are there?), Change Your Brain, Change Your Life fits in perfectly. Filled with "brain prescriptions" (among them cognitive exercises and nutritional advice) that are geared toward readers who've experienced anxiety, depression, impulsiveness, excessive anger or worry, and... |
 | Spark: The Revolutionary New Science of Exercise and the Brain by John J. Ratey A groundbreaking and fascinating investigation into the transformative effects of exercise on the brain, from the bestselling author and renowned psychiatrist John J. Ratey, MD.Did you know you can beat stress, lift your mood, fight memory loss, sharpen your intellect, and function better than ever simply by elevating your heart rate and breaking a sweat? The evidence is incontrovertible: Aerobic... |
 | Driven To Distraction : Recognizing and Coping with Attention Deficit Disorder from Childhood Through Adulthood by Edward M. Hallowell, John J. Ratey This clear and valuable book dispels a variety of myths about attention deficit disorder (ADD). Since both authors have ADD themselves, and both are successful medical professionals, perhaps there's no surprise that the two myths they attack most persistently are: (a) that ADD is an issue only for children; and (b) that ADD corresponds simply to limited intelligence or limited self-discipline.... |
 | The Out-of-Sync Child: Recognizing and Coping with Sensory Processing Disorder, Revised Edition by Carol Stock Kranowitz NEWLY REVISED AND UPDATED The Out-of-Sync Child broke new ground by identifying Sensory Processing Disorder, a common but frequently misdiagnosed problem in which the central nervous system misinterprets messages from the senses. This newly revised edition features additional information from recent research on vision and hearing deficits, motor skill problems, nutrition and picky eaters, ADHA,... |
 | Healing ADD: The Breakthrough Program That Allows You to See and Heal the 6 Types of ADD by Daniel G. Amen Hard, visual data make a compelling case for the existence of attention deficit disorder (ADD) in this pioneering work by Daniel G. Amen, M.D. Using a nuclear medicine technique called "single photon emission computed tomography" (SPECT)--a controversial step, according to some of his peers--Dr. Amen scans patients' brains to identify various abnormalities. From more than 8,000 such studies and... |
 | Delivered from Distraction: Getting the Most out of Life with Attention Deficit Disorder by Edward M. Md Hallowell, John J. Md Ratey Medication? Maybe. Marry the right person and find the right job? A must if you are an adult suffering from ADD (Attention Deficit Disorder). So say psychiatrists Edward M. Hallowell and John J. Ratey, authors of the influential Driven to Distraction, published in 1994. In their new book, Delivered from Distraction, Hallowell and Ratey survey the current medical landscape concerning ADD,... |
 | ADD-Friendly Ways to Organize Your Life by Judith Kolberg, Kathleen Nadeau Organizing books fall short of addressing the unique needs of adults with ADD. They fail to understand the clinical picture of ADD and how it impacts the organizing process often making their advice irrelevant or frustrating when put into application. Books about ADD may address organization/disorganization but do so in a cursory fashion and on a very small scale in what are usually long books... |
 | Screamfree Parenting: The Revolutionary Approach to Raising Your Kids by Keeping Your Cool by Hal Edward Runkel You Can Start a Revolution in Your Family . . . TonightScreamFree Parenting is not just about lowering your voice. It’s about learning to calm your emotional reactions and learning to focus on your own behavior more than your kids’ behavior . . . for their benefit. Our biggest enemy as parents is not the TV, the Internet, or even drugs. Our biggest enemy is our own emotional... |
 | Healing the New Childhood Epidemics: Autism, ADHD, Asthma, and Allergies: The Groundbreaking Program for the 4-A Disorders by Kenneth Bock, Cameron Stauth Autism is an epidemic: It has spiked 1,500 percent in the last twenty years. ADHD, asthma and allergies have also skyrocketed over the same time period. One of these conditions now strikes one in every three children in America. But there is hope. Leading medical innovator Kenneth Bock, M.D., has helped change the lives of more than a thousand children, and in this important book, with a... |
 | The Kid-Friendly ADHD and Autism Cookbook: The Ultimate Guide to the Gluten-Free, Casein-Free Diet by Pamela Compart, Dana Laake The best kid-friendly recipes and guide to the gluten-free milk-free diet for ADHD and Autism.What it is. Why it works. How to do it.The Centers for Disease Control reports significant increases in Autism and ADHD - both affecting primarily boys. The CDC estimates that 1 out of 175 children (age 4 to 17) currently have Autism (300,000). Before 1985, Autism occurred in less than 1 out of 2000.... |
| © 2008 BrightSurf.com |