Data released for once-daily guanfacine extended release trial in children with ADHD数据公布每日一次胍法辛缓释审判小儿多动症

Shire – November 16, 2006 — Shire 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.晴-2006年11月16日-晴Plc公司(纳斯达克:shpgy,LSE的:水电,多伦多:SHQ清楚)今日宣布,每日一次剂量的药品侦查胍法辛缓释剂(额,也称为spd503)选择性干扰素受体激动剂显着改善症状,注意缺陷障碍(ADHD)的儿童在6岁至17岁时,作为单一用药. The phase III trial results were presented today at the 2006 U.S. Psychiatric & Mental Health Congress (USPMHC) annual meeting.第三阶段试验结果今天在2006年美国精神科及心理卫生大会(uspmhc)年度会议. Two additional studies also released at the meeting report the pharmacokinetic profile of guanfacine extended release.另外两项研究也发表在会上报告的药概况胍法辛缓释剂.

Shire submitted a New Drug Application (NDA) for guanfacine extended release on August 24, 2006.晴提交了新药申请(NDA)可用于胍法辛缓释剂于2006年8月24日. 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.如果获得批准,胍法辛缓释剂,它不是刺激中枢神经系统,将首次为每日一次选择性干扰素受体激动剂复方用于治疗儿童多动症.

“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."胍法辛缓释剂研制,使每日一次给药通过控释制定,说:"eliseo萨利纳斯,海事,晴的EVP和首席科学官. “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.”"研究表明,缓释制定胍法辛,有效地提供了一天的多动症的症状控制,以每日单剂量基于几个标准症状的措施."

Monotherapy with Once-Daily Guanfacine Extended Release Significantly Improved ADHD Symptoms单用每日一次胍法辛缓释着改善多动症症状

In this study, investigators randomized 345 subjects to receive placebo or 2 mg, 3 mg or 4 mg guanfacine extended release once daily.在这项研究中,随机调查345名对象接受安慰剂或2毫克,3毫克或4毫克胍法辛缓释剂,每日一次. 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).学习共分三个阶段:筛选(最多14天),白卷(一星期左右停止目前ADHD的药物)和双盲治疗(8周). 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.99.85%做一个被迫剂量地增加胍法辛缓释剂在1毫克递增,每周从1毫克,每天的第一周期间最长以4毫克,每天在四个星期内,五,根据随机化. The guanfacine extended release dose was then decreased at the same weekly rate starting in weeks six and seven.该胍法辛缓释剂随即下跌,在该周刊的速度开始在星期6和7.

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).相比安慰剂孩子6岁至17岁之间治疗胍法辛缓释剂有显着改善的核心症状多动症(多动,冲动,注意力),所反映的总分,对初级效能测试方面,ADHD评定量表(多动症-巴-四). The ADHD-RS-IV is a standard test for diagnosing ADHD in children and adolescents and for assessing their response to treatment.多动症的遥感四是一个标准试验诊断儿童多动症的儿童和青少年,以及评估其对治疗反应. The scale, which contains 18 items, is based on the ADHD diagnosis criteria as defined in the DSM-IV TR, a publication of the American Psychiatric Association.规模,其中包含18项,是基于多动症诊断标准界定DSM-IV的图腾,出版的美国精神病学协会. A reduction in the ADHD-RS-IV score reflects improvement.减少了多动症-巴-四评分反映改善.

Overall, average reductions in ADHD-RS-IV total scores were 16.7 points for guanfacine extended release and 8.9 for placebo (P <.0001).总体而言,平均削减多动症-巴-四总分16.7分胍法辛缓释剂和8.9为安慰剂(磷"0.0001). 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.调查人员指出,在改善多动症-巴-四的成绩,早在两个星期后开始给药,有显着改善,在所有胍法辛缓释剂组发生在第三个星期开始,一直延续到最后评价在每周五. 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.另外,分析体重调整的实际剂量(毫克/公斤)显示减少多动症-巴-四总分从基线的34%至65%胍法辛缓释剂相比,有23%的安慰剂.

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).意义也看到,在各中学疗效措施其中包括分数论临床整体印象改善(类似CGI),临床总体印象严重性(类似CGI),Conners父母家长量表修改:缩写形式(cprsr)和Conners父母'教师评定量表修订版:短形式(报税-R组).

"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."作为第一选择干扰素受体激动剂正在研制的治疗多动症,胍法辛缓释会欢迎我们除了外伤ADHD的药物.在这一临床试验胍法辛缓释着改善多动症症状基于几个标准的应对措施,"注意到从那时梅尔梅德,海事,医务主任的梅尔梅德中心scottsdale,AZ排列. "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.""作为一名医师,我只能说我们的社会一直有意扩大范围,对ADHD的治疗选择须使用方面的一个整体治疗方案,使病人可以得到个性化及优化的照顾."

Guanfacine extended release was generally well-tolerated in this study.胍法辛缓释剂一般都具有良好的耐受性,在这项研究. The most commonly reported treatment-emergent adverse events were somnolence, headache, fatigue, upper abdominal pain, and sedation.最常报告说,治疗中出现的不良事件为嗜睡,头痛,疲劳,上腹疼痛,镇静. Incidence of sedative events (somnolence, sedation and fatigue) were usually mild or moderate in severity.发病事件镇静(嗜睡,镇静,疲劳)通常是轻度或中度严重. Modest decreases in mean systolic and diastolic blood pressure and pulse were reported.温和跌幅,收缩压及舒张压血压和脉搏的报道.

Guanfacine Extended Release Formulation胍法辛缓释制定

Guanfacine extended release, a novel formulation of guanfacine, was developed by incorporating ionic polymers, enteric polymers, and organic acids within the tablet matrix.胍法辛缓释剂,新型制定胍法辛,是发达国家把离子聚合物,肠溶性聚合物,和有机酸的片基. 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.这一提法的目的是控制和延长释放胍法辛,对比眼前的,爆裂式释放提供了市售立即释放(IR)的制定胍法辛,这表明,作为治疗高血压.

About Guanfacine Extended Release约胍法辛缓释

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.Shire说,是寻求批准1毫克,2毫克,2.5毫克,3毫克,3.5毫克和4毫克,每日一次胍法辛缓释剂控制多动症的症状,整个一天孩子6岁至17岁之间. 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.该胍法辛缓释展区包括数据,从两个安慰剂对照试验,在儿童和青少年的年龄6至17个评价复方的疗效和安全性在控制多动症的症状评估一次,每周用多动症量表,其中包括过动/冲动而心不在焉分量.

Guanfacine extended release is a once-daily formulation of the selective alpha-2A-adrenoceptor agonist.胍法辛缓释剂是一次制定每天的选择性干扰素受体激动剂. Unlike some other ADHD treatments, guanfacine extended release is not a central nervous system stimulant or a controlled substance.不像其他一些治疗多动症,胍法辛缓释不是刺激中枢神经系统或控制物质.

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.肾上腺素受体存在于几乎所有类型的细胞在体内充当受体两种神经递质,肾上腺素(肾上腺素)和去甲肾上腺素,用神经细胞进行沟通. An agonist is a molecule that acts similar to these neurotransmitters by also binding to receptors.激动剂,是一种分子,类似的行为,这些神经递质也结合受体. 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.  Full press release about extended release guanfacine can be found here:它是假设,盐酸胍法辛绑定了干扰素-肾上腺素受体细胞直接采取行动,在该部分的大脑前额叶皮层,这是一个与工作记忆,行为抑制,注意力和认知控制,以及能力配器的思想和行动.充分新闻稿约缓释胍法辛可发现这里:

Extended-release guanfacine for children with ADHD缓释胍法辛为小儿多动症

Editorial note:  Guanfacine, which used to be known by the now defunct brand name of Tenex, is well-known to child and adolescent psychiatrists as an effective “second-line,” non-stimulant medication for ADHD, but is lesser known to the general public.  Shire’s studies completed in hopes of FDA approval (a likely outcome) will provide better controlled clinical data in children than we have had on this ADHD medication before.  A word of caution, however, is needed.  An older study of guanfacine’s use for ADHD in children who had a parent with bipolar disorder showed a worrisome occurrence of manic-like symptoms in some of these children when placed on guanfacine.  It is likely that children at risk for bipolar disorder were not placed in Shire’s ADHD clinical trial; therefore, our knowledge regarding the use of guanfacine for ADHD where there is a family history of bipolar disorder is limited — Dr. Z.编者按:胍法辛,而这本来是人所共知的,现在停业品牌TENEX俄罗斯,众所周知,以儿童和青少年心理作为一个有效的"第二线",非兴奋剂药物治疗多动症,但较轻的,是为公众所熟知.晴的学业完成后,希望FDA批准(其中一个可能的结果)为更好地控制临床资料儿童比我们已就这个多动症前用药.一言谨慎然而,需要进一步的研究.一名年纪较大的研究胍法辛的使用多动症儿童因父母与双相情感障碍表现令人担忧的发生躁狂样症状,其中部分孩子放在胍法辛.它有可能使儿童风险双极紊乱不处于晴的多动症临床试验;因此,我们的知识,对于使用胍法辛多动症有家族病史的双相情感障碍是有限博士宜