Dextroamphetamine

*仅供医学专业人士阅读参考从几年前到现在，不少新闻都报道了“聪明药”的滥用，传说中，“聪明药”可以让人更专注，不怎么休息也能长时间保持头脑清醒和思维敏捷，所以会有学生在重要考试前夕服用。实际上，这些“聪明药”主要就是治疗注意缺陷/多动障碍（ADHD）的中枢兴奋剂类药物，例如哌甲酯和安非他明，即使前者是我国一类管制精神类药品，后者在我国尚未批准上市，也挡不住一些违规处方和代购。但是，中枢兴奋剂类药物也有相应的不良反应，包括头晕、头痛、失眠、眩晕、心悸和胃肠道反应等。甚至安非他明由于显著增加突触前多巴胺释放量，与精神疾病患者中观察到的现象一致，而存在增加精神疾病风险的担忧。在最近的《美国精神病学杂志》上，美国麦克莱恩医院的研究团队通过病例对照研究揭示，与过去一个月内未服用相比，服用安非他明与精神疾病和躁狂症风险增加168%有关，且存在剂量反应关系，高剂量（＞30mg右旋安非他明当量）与风险增加428%有关，相比之下，服用哌甲酯则与风险增加无关[1]。这项研究使用麻省总医院百瀚医疗系统（MGB）的电子医疗记录数据，纳入了2005-2019年间在麦克莱恩医院首次因精神疾病或躁狂症入院的16-35岁患者作为病例组，研究人员为每位患者匹配了2名没有精神疾病和躁狂症史，因抑郁和/或焦虑障碍入院的患者作为对照组。病例组和对照组分别纳入了1374例和2748例患者，病例组中，60.6%因精神疾病入院，28.2%因有精神疾病特征的发作性躁狂症入院，11.1%因无精神疾病特征的发作性躁狂症入院。研究筛选流程和最终入组人数在过去一个月中，有415例参与者服用过安非他明，病例组和对照组分别为204例和211例，病例组报告非处方中枢兴奋剂类药物滥用的更多，但大多数参与者仍然是通过处方获取安非他明的（病例组和对照组分别为79.4%和89.1%）。在校正了人口统计学因素、基础精神疾病、精神类药物和家族史因素后，研究人员发现，与未服用相比，过去一个月内服用安非他明与精神疾病和躁狂症风险增加168%有关，且存在剂量反应关系，低（≤15mg）、中（＞15至30mg）和高（＞30mg）剂量分别与风险增加79%、251%和428%有关。病例组与对照组在过去一个月内服用安非他明的情况和精神疾病/躁狂症风险在精神疾病和躁狂症的风险归因占比方面，任意剂量的处方安非他明为62.7%，高剂量为81.0%。研究人员还发现，在≤22岁的参与者中，安非他明的影响小于＞22岁的参与者，风险增加分别为126%和310%。在不同性别中没有这样的差异。在过去一个月内，病例组和对照组分别有37例和102例参与者服用哌甲酯，与未服用相比，服用哌甲酯与精神疾病和躁狂症的风险增加无关，参与者的哌甲酯服用剂量显著低于安非他明（平均右旋安非他明当量：哌甲酯为18.1mg，安非他明为25.2mg）。综上所述，服用安非他明与精神疾病和躁狂症的风险显著增加有关，并且风险会随着剂量的升高而升高，而哌甲酯与风险增加无关。这一结果与此前一项大型队列发现的，安非他明相比哌甲酯与精神疾病风险增加有关[2]相一致。研究人员指出，中枢兴奋剂类药物的标签上没有剂量上限，为患者开具的药物剂量主要取决于医生对病情严重程度的判断，但根据本研究的结果，精神疾病和躁狂症的风险会随药物剂量增加，需要引起注意。至于想要尝试“聪明药”的朋友，最好也还是收手吧~参考文献：[1] Moran L V, Skinner J P, Shinn A K, et al. Risk of Incident Psychosis and Mania With Prescription Amphetamines[J]. American Journal of Psychiatry, 2024: appi. ajp. 20230329.[2] Moran L V, Ongur D, Hsu J, et al. Psychosis with methylphenidate or amphetamine in patients with ADHD[J]. New England Journal of Medicine, 2019, 380(12): 1128-1138.本文作者丨应雨妍

Phase 3 Data Collected to Date Sufficient for Submission of New Drug Application CTx-1301 Could Benefit >60% of ADHD Patients Currently Using Immediate-Release Booster Doses Advancing Discussions with Commercialization Partners Ready to Engage with Payers for Reimbursement and Market Access KANSAS CITY, Kan., May 21, 2024 (GLOBE NEWSWIRE) -- Cingulate Inc. (NASDAQ: CING), a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, announced that it has received confirmation from and is aligned with the U.S. Food and Drug Administration (FDA) on the requirements necessary for filing a New Drug Application (NDA) for its lead Phase 3 candidate CTx-1301 (dexmethylphenidate), for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients six years of age or older. Details from the FDA communication to Cingulate include the following: Per the 505(b)(2) pathway, submission of CTx-1301’s NDA does not require continuation of the fixed dose study and the onset and duration study; Data collected to date from these two Phase 3 studies will be included in the filing; and Contemporaneously with the preparation of the NDA filing, Cingulate will conduct a Phase 1 fed/fast study, the study is expected to last approximately two to three weeks, with the results being included in the NDA filing. “We are pleased with the FDA’s guidance and perspective regarding our pathway to a timely NDA filing, and we will proceed to complete all remaining requirements accordingly,” said Cingulate Chairman and CEO Shane J. Schaffer. “We also believe this communication provides additional go-to-market momentum as we continue to meet with potential partners for the outlicensing of CTx-1301 in the United States and abroad. Now that we have a clear path to submission, we look forward to engaging with key payer stakeholders to achieve maximum access and market penetration to benefit ADHD patients and their families.” Cingulate has begun NDA preparation and expects to submit its filing in the first half of 2025. Ann Childress, M.D., President, Center for Psychiatry and Behavior Medicine, Inc., and lead investigator of Cingulate’s CTx-1301 onset and duration study, stated, “The treatment effect size of CTx-1301 was remarkable given the current effect sizes observed in the marketplace. Many patients require longer duration of efficacy and must add a second, or booster, dose to ensure treatment effect over their entire active day. The patients I observed, once notified they were taking CTx-1301, have expressed a desire to remain on the medication after the trial concluded.” “If approved,” Childress continued, “I believe CTx-1301 could potentially benefit the more than 60 percent of patients currently using immediate-release booster doses to extend the efficacy of their medications.” Earlier this year, Cingulate presented results from the Phase 3 adult efficacy and safety study of CTx-1301 at the 2024 American Professional Society of ADHD and Related Disorders (APSARD) conference in Orlando, FL. The results were previously presented at the 2023 Psych Congress, where a poster describing the data was selected as a finalist for the Psych Congress’s First Annual Poster Awards. The Cingulate poster presented at APSARD provided additional insight regarding CTx-1301’s ADHD leading effect size. Effect size conveys clinical significance rather than statistical significance, is not reliant on sample size, and allows for comparison across trials. The poster presented may be viewed here. About Attention Deficit/Hyperactivity Disorder (ADHD) ADHD is a chronic neurobiological and developmental disorder that affects millions of children and often continues into adulthood. The condition is marked by an ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development. In the U.S., approximately 6.4 million children and adolescents (11 percent) aged under the age of 18 have been diagnosed with ADHD. Among this group, approximately 80 percent receive treatment, with 65-90 percent demonstrating clinical ADHD symptoms that persist into adulthood. Adult ADHD prevalence is estimated at approximately 11 million patients (4.4 percent), almost double the size of the child and adolescent segment combined. However, only an estimated 20 percent receive treatment. About CTx-1301 Cingulate’s lead candidate, CTx-1301, utilizes Cingulate’s proprietary PTR drug delivery platform to create a breakthrough, multi-core formulation of the active pharmaceutical ingredient dexmethylphenidate, a compound approved by the FDA for the treatment of ADHD. Dexmethylphenidate is part of the stimulant class of medicines and increases norepinephrine and dopamine activity in the brain to affect attention and behavior. While stimulants are the gold standard of ADHD treatment due to their efficacy and safety, the long-standing challenge continues to be providing patients with an entire active-day duration of action. CTx-1301 is designed to precisely deliver three releases of medication at the predefined time, ratio, and style of release to optimize patient care in one tablet. The result is a rapid onset and entire active-day efficacy, with the third dose being released around the time when other extended-release stimulant products begin to wear off. About Precision Timed Release™ (PTR™) Platform Technology Cingulate is developing ADHD and anxiety disorder product candidates capable of achieving true once-daily dosing using Cingulate’s innovative PTR drug delivery platform technology. It incorporates a proprietary Erosion Barrier Layer (EBL) providing control of drug release at precise, pre-defined times with no release of drug prior to the intended release. The EBL technology is enrobed around a drug-containing core to give a tablet-in-tablet dose form. It is designed to erode at a controlled rate until eventually the drug is released from the core tablet. The EBL formulation, Oralogik™, is licensed from BDD Pharma. Cingulate intends to utilize its PTR technology to expand and augment its clinical-stage pipeline by identifying and developing additional product candidates in other therapeutic areas in addition to Anxiety and ADHD where one or more active pharmaceutical ingredients need to be delivered several times a day at specific, predefined time intervals and released in a manner that would offer significant improvement over existing therapies. To see Cingulate’s PTR Platform, click here. About Cingulate® Cingulate Inc. (NASDAQ: CING), is a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, designed to improve the lives of patients suffering from frequently diagnosed conditions characterized by burdensome daily dosing regimens and suboptimal treatment outcomes. With an initial focus on the treatment of attention deficit/hyperactivity disorder (ADHD), Cingulate is identifying and evaluating additional therapeutic areas where PTR technology may be employed to develop future product candidates, including to treat anxiety disorders. Cingulate is headquartered in Kansas City. For more information visit Cingulate.com. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include all statements, other than statements of historical fact, regarding our current views and assumptions with respect to future events regarding our business, including statements with respect to our plans, assumptions, expectations, beliefs and objectives with respect to product development, clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. These statements are generally identified by the use of such words as “may,” “could,” “should,” “would,” “believe,” “anticipate,” “forecast,” “estimate,” “expect,” “intend,” “plan,” “continue,” “outlook,” “will,” “potential” and similar statements of a future or forward-looking nature. Readers are cautioned that any forward-looking information provided by us or on our behalf is not a guarantee of future performance. Actual results may differ materially from those contained in these forward-looking statements as a result of various factors disclosed in our filings with the Securities and Exchange Commission (SEC), including the “Risk Factors” section of our Annual Report on Form 10-K filed with the SEC on April 1, 2024. All forward-looking statements speak only as of the date on which they are made, and we undertake no duty to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law. Investor Relations Thomas Dalton Vice President, Investor & Public Relations, Cingulate TDalton@cingulate.com 913-942-2301 Matt Kreps Darrow Associates mkreps@darrowir.com 214-597-8200 A photo accompanying this announcement is available at Cingulate's Precision Timed Release Technology™ (PTR™) Platform Technology Cingulate® is developing ADHD product candidates capable of achieving true once-daily dosing using the Company’s innovative Precision Timed Release™ (PTR™) drug delivery platform technology incorporating a proprietary Erosion Barrier Layer (EBL) that provides control of drug release at precise, pre-defined times with no release of drug prior to the intended release.The technology is an erodible barrier layer that is wrapped around a drug containing core to give a tablet-in-tablet dose form. The barrier layer is designed to erode at a controlled rate until eventually the drug is released from the core tablet.CTx-1301 (dexmethylphenidate) and CTx-1302 (dextroamphetamine) have pioneering compression technology with specialized release characteristics that may enable patients to take one tablet per day and avoid the use of additional immediate release “boosters.”We believe our most advanced drug product candidate, CTx-1301, will be the first true once-daily dexmethylphenidate tablet