查看完整版本: 实验性口吃药物“班科龙（PAGOCLONE）”的效果让人充满希望！

实验性口吃药物“班科龙（PAGOCLONE）”的效果让人充满希望！

[SIZE="3"][SIZE="5"][B]INDEVUS ANNOUNCES PROMISING PHASE II DATA FOR PAGOCLONE IN STUTTERING

制药公司INDEVUS宣布“派格克隆（PAGOCLONE）“的药物临床试验第二阶段的结果很棒，让人们对这种新药在口吃治疗领域的前途充满希望！[/B][/SIZE]

北京协会的严畅把上面的英文内容译成了中文. 让我们向严畅表示衷心的感谢!

严畅的话：应火鸟的要求，现将登在口吃基金会论坛上有关治疗口吃的药物的文章翻译如下。在此，我需要申明的是，我本人并不赞成用药物治疗口吃，但了解一些治疗口吃的药物及其原理对我们认识口吃是有帮助的。这也是我答应火鸟要求的原因。

虽然如此，我仍然劝大家在使用药物时需慎重，一是因为“凡药三分毒”，在我看来，不管是哪种药物，只要是西药，就肯定会有副作用。二是因为持续用药会对药物产生一种依赖，而且随着用药时间的延长，一般来说，药效也会降低。所以，矫正口吃最好不要借助于药物。

派格克隆（pagoclone）在一期和二期试验中疗效显著，且适用面广

莱克星顿，马萨诸塞州，2006年5月24日

英德威斯（Indevus）药品有限公司（纳斯达克股市上的代码是IDEV）今天宣布该公司对派格克隆的二期临床试验取得了可喜的成果。试验结果显示，与安慰剂相比，派格克隆在一期和二期试验中都产生了良好的效果。另外，与安慰剂相比，不管在一期，还是在二期，派格克隆要么改善了口吃者的各项口吃指标，要么使口吃者出现了症状明显改善的趋势。试验表明，派格克隆适用面广，且不会引发明显的负面症状。

名为“快速研究”的二期试验是一个为期8周、兼用安慰剂、多中心的双盲测试（双盲测试是指测试者和被测试者对有关试验的细节均无所知）。试验者随机抽取了 132个病人，其中88个病人服用派格克隆，剂量从每天0.3毫克逐渐增加到每天0.6毫克。44位病人服用安慰剂。79%的病人是男性，这也反映了口吃病患者的男女比例。

由于研究成果令人振奋，该公司计划在二期试验的总结会上邀请美国食品药品监督管理局的官员参加，与他们讨论研究成果和下一步的研究计划。

“英德威斯公司已经完成了药物测试，据我们所知，这是有史以来关于口吃的最大范围的一次测试，结果非常令人兴奋，”英德威斯公司董事会主席、总裁及首席执行官、医学博士Glenn L. Cooper说，“结果显示，口吃，这一目前尚无药物可以治愈的疾病，用派格克隆有可能治愈。这次的研究是作为一项探索性试验被设计的，它是第一期焦虑测试的继续。‘快速测试’使我们有可能从临床观察诊断的角度来评价派格克隆的疗效，我们相信，这为我们今后制定下一步的临床试验计划奠定了基础。”

加州大学精神病学系副教授、医学博士Gerald A. Maguire说，“作为一个口吃者和研究、治疗口吃的内科医生，我对这次试验的结果感到非常兴奋。作为这项研究的调查者，我亲眼看到派格克隆对病人生活的积极影响。我的病人服过派格克隆以后，有一半以上的人，其口吃程度减轻了，这与试验的整体结果是一致的。虽然口吃无法治愈，但派格克隆作为一种适用面广、有效且可行的药物，为成千上万的美国口吃者带来了希望。”

对一期试验效果的检测有以下几个指标：口吃频率和时间长度指标（SSI-3）、口吃严重程度指标（SEV）和主观掩饰口吃指标（SSS）。

SSI-3是一项已被证实为有效的口吃测量指标。研究小组成员在第4周和第8周分别对病人作了测试，他们录下了病人与人交谈和朗读的声音，然后把这些资料汇总到中央实验室进行分析。分析人员对病人的情况毫不知情。口吃的频率和长度是通过计算口吃音节占说出的所有音节以及阻塞时间占全部说话时间的比例而得出来的。口吃者的口吃程度在不同的时间会有所不同。因此，在治疗前和治疗中我们都收集了两组数据。分析结果显示，服用派格克隆的患者，其口吃频率和时间长度都大大低于服用安慰剂的患者。

SEV指标也是一项被证实为有效的指标，它用数值来表示口吃的严重程度，0代表“完全没有口吃”，9代表“极端严重的口吃”。研究人员在第2周、第4周和第8周三次收集了SEV指标。分析结果显示，服用派格克隆的病人其SEV指标要低于服用安慰剂的患者。

SSS指标是一项被证实为有效、由病人打分的评价指标，它考虑到了具体的说话环境。与服用安慰剂的病人相比，服用派格克隆的病人在第2周和第4周其SSS指标有明显改善，到第8周时则出现了显著改善的趋势。

对二期试验结果的检测使用了以下几项指标：临床全球印象改善（CGI-I）、列博维茨（Liebowitz）社会焦虑（LSAS）和言语自然度（SNS）。

CGI-I指标在第2周、第4周和第8周时收集了三次，它是一项7分制的指标，目前已被证实为有效并被广泛接受。这项指标由医生打分，它把可以得到的有关病人的所有临床信息都考虑在内，主要用于测量口吃的改善程度。到第8周时，服用派格克隆的病人有55%这项指标得到了改善，而服用安慰剂的病人只有36% 得到了改善。

LSAS指标在第4周和第8周时收集了两次，它是一项衡量社会焦虑程度的指标。口吃常常会加重社会焦虑程度。虽然患有严重焦虑症的病人被排除在试验之外，但试验结果仍表明，派格克隆能有效缓解病人的社会焦虑程度。

试验结果表明，派格克隆是一种安全的、适用面广的药物，服用派格克隆不会引发严重的负面症状。服用者反映最多的负作用是头痛（派格克隆12.5%，安慰剂 6.8%）和困倦（派格克隆8%，安慰剂0%）。就目前服用者所反映的情况来看，派格克隆和安慰剂在使服用者嗜眠和镇静的副作用方面是类似的。另外， SNS指标显示，服用派格克隆对口吃者言语的自然度没有负面影响。

派格克隆是一种新型的γ-氨基丁酸A型选择性受体调节剂，它不含苯二氮卓（一种用于制造各种镇静剂的化合物，它有使人过度镇静、情绪冷漠的副作用）。据信，γ-氨基丁酸是人脑中的一种重要的神经传递素，而口吃者大脑中的γ-氨基丁酸很容易受到干扰。派格克隆能增强大脑中γ-氨基丁酸的活力，从而起到维持大脑中控制言语部分的正常功能。

想了解更多关于英德威斯的信息，请登陆[url]www.indevus.com。[/url]

想了解更多关于派格克隆的信息，请登陆[url]www.stutteringstudy.com。[/url]

下面是英文原文：

Compound Achieves Multiple Primary and
Secondary Endpoints and is Well-Tolerated

LEXINGTON, MA, May 24, 2006 – Indevus Pharmaceuticals, Inc. (NASDAQ: IDEV) today announced top line results from the Company’s Phase II clinical trial for pagoclone in persistent developmental stuttering. Results from the trial show that pagoclone produces a statistically significant benefit in multiple primary and secondary endpoints compared to placebo. Additionally, pagoclone produced either numerically superior improvement or trends for significant improvement on virtually all other primary and secondary endpoints when compared to placebo.  Pagoclone was also shown to be well tolerated and not associated with any serious adverse events.

The Phase II trial, known as the EXPRESS study, was an 8-week, placebo controlled, double-blind, multi-center trial with an open label extension.  There were a total of 132 patients randomized in the trial.  Eighty-eight patients received escalating doses of pagoclone from 0.3 mg to 0.6 mg per day. Forty-four patients received placebo.  Seventy-nine percent of the patient population was male which is reflective of the gender distribution of this disorder.  

As a result of the promising outcome of this study, the Company plans to meet with the FDA in an End of Phase II meeting to discuss the findings and its plans for further clinical development.  

“Indevus has completed what we believe is the largest pharmaceutical trial ever conducted for stuttering and the results are very exciting,” stated Glenn L. Cooper, M.D., chairman, president and chief executive officer of Indevus.  “Our results today show that stuttering, a condition with no approved pharmacological treatment, is potentially treatable with pagoclone. This study was designed as an exploratory trial to follow up on a limited number of observations of the effect of pagoclone on stuttering during previous anxiety trials.  The design of the EXPRESS trial enabled us to evaluate the condition from several clinical perspectives and we believe this provides us with a strong foundation to develop a clinical plan for further development.”   

Gerald A. Maguire, M.D., associate professor, department of psychiatry, University of California, Irvine School of Medicine, stated, “Being a person who stutters and a physician who researches and treats stuttering, I am very excited about the results of this trial.  As an investigator on this study, I saw first hand the positive impact pagoclone can have on the lives of patients.  Consistent with the results of the entire study sample, more than half of my pagoclone treated patients had a clinically meaningful decrease in the severity of their stuttering.  Although there is no cure for stuttering, pagoclone holds significant promise as a well-tolerated, effective and viable treatment for the millions of Americans who stutter.”  

The primary endpoints evaluated in the double-blind, phase of the study were the Frequency and Duration Subscale of the Stuttering Severity Instrument Version 3 (SSI-3), the Stuttering Severity Scale (SEV) and the Subjective Screening of Stuttering (SSS) Severity Subscore. Given that this was an exploratory study, pre-specified analyses utilized 1-tailed tests of significance.  

The SSI-3 is a validated measure of stuttering. During study visits at week 4 and week 8, patients were videotaped while engaged in both a conversational and reading task. The videotapes were analyzed and scored at a central laboratory.  Raters were blinded with regard to treatment and visit. The frequency and duration subscales were calculated by measuring the proportion of syllables stuttered compared to syllables spoken and the length of time of each stuttering block or event.  The variability of stuttering naturally tends to wax and wane over time. Accordingly, two data points were collected prior to treatment and two data points were collected while on treatment at week 4 and week 8 to determine the on-treatment effect of pagoclone. The on-treatment effect of pagoclone was shown to produce a statistically significant reduction in the frequency and duration of stuttering as measured by the SSI-3 scale when compared to placebo (p=.02).  

The SEV, measured at week 2, week 4 and week 8, is a validated measure of stuttering.  The SEV is a 9-point, clinician rated severity scale anchored by “no stuttering” and “extremely severe stuttering”. The on-treatment effect of patients receiving pagoclone demonstrated a numerically superior rating versus patients treated with placebo (p=.18).

The SSS Severity Subscore, measured at week 2, week 4 and week 8, is a validated, patient-rated assessment of stuttering that takes into account specific speaking situations that have taken place over the prior week. Pagoclone produced a statistically significant reduction at week 2 (p=.004) and week 4 (p=.05) and a trend for significant improvement at week 8 (p=.08) as compared to placebo.  

The secondary endpoints evaluated in the study included the Clinician Global Impression-Improvement (CGI-I), the Liebowitz Social Anxiety Scale (LSAS) and the Speech Naturalness Scale (SNS).  

The CGI-I, measured at week 2, week 4 and week 8, is a 7-point, validated and widely accepted clinician-rated measure of improvement as compared to baseline, considering all sources of available clinical information about the patient. For analysis of the improvement in the severity of stuttering, patients were categorized as having either “improved” versus “no change or worsened”.  Pagoclone produced numerically superior improvement at week 2 (p=.20) and statistically significant improvement at week 4 (p=.007) and at week 8 (p=.02) as compared to placebo. At week 8, 55% of pagoclone treated patients were improved compared to 36% of placebo treated patients.  

The LSAS, measured at week 4 and week 8, is a validated measure of social anxiety symptoms.  Stuttering is often co-morbid with symptoms of social anxiety which can be a disabling consequence of stuttering. Although patients with primary anxiety disorders were excluded from participating in the trial, pagoclone produced a trend for significant improvement in social anxiety symptoms (total LSAS score) compared to placebo at week 4 (p=.09) and week 8 (p=.07).  On a subscale comprised of the elements of the LSAS that evaluate anxiety-provoking speaking situations, pagoclone produced statistically significant improvement at both week 4 (p=.02) and week 8 (p=.02).

Pagoclone was shown to be safe and well-tolerated. There were no serious adverse events associated with pagoclone.  The most commonly reported side effects associated with pagoclone were headache (12.5% for pagoclone and 6.8% for placebo) and fatigue (8% for pagoclone and 0% for placebo). As with all prior trials for pagoclone, reports of somnolence and sedation were similar between pagoclone and placebo. Additionally, pagoclone exerted its clinical effect on patients without disrupting the naturalness of their speech as assessed by the SNS, a validated 9-point scale.   

Approximately 90% of patients continued into the open-label phase of the study in which all patients receive pagoclone. Early results of the open-label phase indicate that patients initially randomized to pagoclone have continued to show improvement in their stuttering and those initially randomized to placebo, and now receiving pagoclone, are exhibiting improvement in their condition.

Pagoclone is a novel, non-benzodiazepine, GABA-A selective receptor modulator. It is part of a new chemical class of agents and lacks many of the common benzodiazepine side effects such as sedation and withdrawal. The precise mechanism of action is unknown however, GABA is believed to be an important neurotransmitter in the brain that may be disrupted in people who stutter.  Pagoclone enhances the activity in GABA circuits in the brain and thus may help restore more normal function in speech areas of the brain.  

Nearly 3 million Americans, or approximately 1% of the adult population, are afflicted with stuttering, with more than 4 times as many males being affected by the condition as females.  Stuttering is a DSM-IV-TR Axis I disorder and is characterized by symptoms in which the flow of speech is disrupted by prolongations, repetitions, and blocks of sounds, syllables, words or phrases.  The exact cause of stuttering is unknown; however, emerging evidence has shown that this disorder is associated with abnormalities in the brain areas related to speech motor control. Stuttering most often begins in early childhood and often persists into adulthood and this form is classified as persistent developmental stuttering. Given the importance of communication in daily life, stuttering can often impair an individual’s academic, social and occupational functioning. No medication is FDA approved for stuttering and the most commonly utilized treatment is speech therapy.   

Indevus Pharmaceuticals is a biopharmaceutical company engaged in the acquisition, development and commercialization of products targeting certain medical specialty areas, including urology, gynecology and men's health. The Company currently markets SANCTURA® for overactive bladder and DELATESTRYL® for the treatment of male hypogonadism. The Company has multiple compounds in clinical development, including SANCTURA XR™, the once-daily formulation of SANCTURA, NEBIDO® for the treatment of male hypogonadism, PRO 2000 for the prevention of infection by HIV and other sexually transmitted pathogens, IP 751 for interstitial cystitis, pagoclone for stuttering, and aminocandin for systemic fungal infections.   

For more information on Indevus, please visit [url]www.indevus.com[/url].  

For more information on pagoclone and stuttering, please visit [url]www.stutteringstudy.com[/url].



Except for the descriptions of historical facts contained herein, this press release contains forward-looking statements that involve risks and uncertainties that could cause the Company's actual results and financial condition to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties are set forth in the Company's filings under the Securities Act of 1933 and the Securities Exchange Act of 1934 under "Risk Factors" and elsewhere, and include, but are not limited to: dependence on the success of SANCTURA(R) and SANCTURA XR(TM); the early stage of products under development; uncertainties relating to clinical trials, regulatory approval and commercialization of our products, particularly SANCTURA, SANCTURA XR and NEBIDO(R); risks associated with contractual agreements, particularly for the manufacture and co-promotion of SANCTURA and SANCTURA XR; dependence on third parties for manufacturing, marketing and clinical trials; competition; need for additional funds and corporate partners, including for the development of our products; failure to acquire and develop additional product candidates; history of operating losses and expectation of future losses; product liability and insurance uncertainties; risks relating to the Redux-related litigation; our reliance on intellectual property and having limited patients and proprietary rights; dependence on market exclusivity; valuation of our Common Stock; risks related to repayment of debts; risks related to increased leverage; and other risks. [/SIZE]

人生转折点跟帖:
本人使用小剂量安定或舒乐安定（半粒——一粒qn)间断使用对口吃并发严重心里障碍取得满意效果，可与其他疗法联合使用，可以很好的改善心态，随着心态的改善口吃减轻，副作用不要担心，100粒一顿也吃不死人，你可以去问一问60岁以上的老人有多少人吃过安定，出现过什么副作用.安定的副作用要看你使用剂量的大小，还看你使用的时间长短，本人主张小剂量间断服用，心态较佳时不需服药。安定是一个经典老药，物美价廉，容易获得。pagoclone不是也有头痛、嗜睡的副作用吗？

［此帖子已被 人生转折点 在 2006-07-14 18:08:36 编辑过］

:) 感谢严畅为我们翻译这篇文章！

另外我要提一句，严畅说的要谨慎用药的观点是完全正确的。不过这个药物还处在试验阶段，我想在中国是没有人能够得到这个药物的。

另外，人生转折点的话我只能理解为对于药物使用的无知了！我不知道你是干什么的，有什么资格来对他人的用药做出推荐！

谢谢愚公把这篇文章的翻译转贴到了这里，为了方便大家的阅读，我把翻译和原文整合在了一起。

吃安定可以减轻？我想试试看

各位，再提醒一次，精神类药物是不能随便吃的，像安定一类的老药物也不行！

期待着奇迹的出现！

我从来不相信奇迹,因为我只相信我自己.我相信我可以通过自己的努力获得自己应该得到的,应该享有的自由.我可以比别人努力100倍来获得别人努力才能获得的东西,包括言语自由和爱情.

没想到我是真实者口吃论坛的第三位真实口吃者,一直没来支持童大哥支持真实者口吃论坛,非常遗憾.主要是自己不太喜欢上网,除非要查资料,再加上室友要打游戏,占着寝室唯一的宽带接口.
其实很不愿意说这些理由....
最近说话一直不太顺畅,甚至不如以前那般流利了.不知道是什么原因.以前一直都能把话说完整,现在却有时候却不能说完整.但是自信却增加了不少,自己已经和很多人说了自己有口吃,一些好朋友.在他们面前说话也不再畏缩着,不发言.
不知道这是好事还是坏事.

刚才浏览了一下童大哥的有关道歉的帖子,虽然不知道什么原因导致论坛那么长时间没开,但还是支持童大哥.能够站出来支持这项事业就是我敬佩的人.

八贯，我的问题在于想做的事情太多了，我想把每一件事情做好，结果却最终什么都没有做好。前段时间在家里觉得自己好像是荒废了很多时光，到头来是百忙一场，所以整个人都消沉下去了……

如果这种药物会面世的话，那会很大的减轻我们口吃患者的痛苦。但是精神类药物都是有依赖性的，特别是对我们口吃患者来说。如果药效慢慢耐受的话，那简直就是等于慢性自杀了。因为我们宁愿这样也不想口吃，至少我是这样认为的。