The combination drug composed of aroxybutynin and atomoxetine, designated AD109, is being developed by Apnimed for the treatment of obstructive sleep apnea (OSA). The present study is a Phase 3 open label continuation protocol enrolling qualifying participants who completed one of the parent Phase 3 double-blind placebo-controlled studies, APC-APN-304 or APC-APN-305.

开始日期2024-07-03

申办/合作机构

Apnimed, Inc.

NCT06400615

/ Completed临床2期

Phase 2 Safety, Efficacy and, Tolerability of Fixed Dose Combination of Aroxybutynin/Atomoxetine (AD109) in Obstructive Sleep Apnea Patients Taking Tirzepatide, Semaglutide or Liraglutide

开始日期2024-05-20

申办/合作机构

Apnimed, Inc.

NCT05813275

/ Completed临床3期

Phase 3 Randomized Double-Blind Placebo-Controlled 6-month Parallel-Arm Study to Compare a Fixed Dose Combination of Aroxybutynin/Atomoxetine (AD109) to Placebo in Obstructive Sleep Apnea (SynAIRgy Study)

This is a Phase 3 Randomized Double-Blind Placebo-Controlled 6-month Parallel-Arm Study to Compare a Fixed Dose Combination of AD109 to Placebo in Obstructive Sleep Apnea.

开始日期2023-09-16

申办/合作机构

Apnimed, Inc.

100 项与 Aroxybutynin/Atomoxetine 相关的临床结果

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100 项与 Aroxybutynin/Atomoxetine 相关的转化医学

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100 项与 Aroxybutynin/Atomoxetine 相关的专利（医药）

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项与 Aroxybutynin/Atomoxetine 相关的文献（医药）

2023-12-15·American Journal of Respiratory and Critical Care Medicine

The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial

Article

作者: Abaluck, Brian ; Schweitzer, Paula K ; Rosenberg, Russell ; Ojile, Joseph M ; Sangal, R Bart ; Drake, Christopher L ; Corser, Bruce ; Maynard, James ; Taranto-Montemurro, Luigi ; Thein, Stephen G

Rationale: Obstructive sleep apnea (OSA) is a common sleep disorder for which the principal treatment option, continuous positive airway pressure, is often poorly tolerated. There is currently no approved pharmacotherapy for OSA. However, recent studies have demonstrated improvement in OSA with combined antimuscarinic and noradrenergic drugs. Objectives: The aim of this study was to evaluate the efficacy and safety of AD109, a combination of the novel antimuscarinic agent aroxybutynin and the norepinephrine reuptake inhibitor atomoxetine, in the treatment of OSA. Methods: Phase II randomized, double-blind, placebo-controlled, parallel-group, 4-week trial comparing AD109 2.5/75 mg, AD109 5/75 mg, atomoxetine 75 mg alone, and placebo (www.clinicaltrials.gov identifier NCT05071612). Measurements and Main Results: Of 211 randomized patients, 181 were included in the prespecified efficacy analyses. Sleep was assessed by two baseline and two treatment polysomnograms. Apnea-hypopnea index with a 4% desaturation criterion (primary outcome) was reduced from a median (IQR) of 20.5 (12.3-27.2) to 10.8 (5.6-18.5) in the AD109 2.5/75 mg arm (-47.1%), from 19.4 (13.7-26.4) to 9.5 (6.1-19.3) in the AD109 5/75 mg arm (-42.9%; both P < 0.0001 vs. placebo), and from 19.0 (11.8-28.8) to 11.8 (5.5-21.5) with atomoxetine alone (-38.8%; P < 0.01 vs. placebo). Apnea-hypopnea index with a 4% desaturation criterion decreased from 20.1 (11.9-25.9) to 16.3 (11.1-28.9) in the placebo arm. Subjectively, there was improvement in fatigue with AD109 2.5/75 mg (P < 0.05 vs. placebo and atomoxetine). Atomoxetine taken alone decreased total sleep time (P < 0.05 vs. AD109 and placebo). The most common adverse events were dry mouth, insomnia, and urinary hesitancy. Conclusions: AD109 showed clinically meaningful improvement in OSA, suggesting that further development of the compound is warranted. Clinical trial registered with www.clinicaltrials.gov (NCT05071612).

2022-12-01·Journal of Clinical Sleep Medicine

Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA

Article

作者: Abaluck, Brian ; Thein, Stephen ; Rosenberg, Russell

STUDY OBJECTIVEObstructive sleep apnea is a common and serious sleep disorder for which treatment remains challenging due to lack of adherence to approved therapies. Previous pharmacological studies addressing sleep-related upper airway muscle hypotonia suggested that the combination of atomoxetine and oxybutynin is effective in treating obstructive sleep apnea. The current study is with aroxybutynin (AD109), a new enantiomerically pure form of oxybutynin with better safety profile compared to racemic oxybutynin.METHODSThis was a randomized, double-blind, placebo-controlled, crossover study in patients with mild to moderate obstructive sleep apnea. Each received low-dose AD109 (37.5/2.5 mg), high-dose AD109 (75/2.5 mg), and placebo at bedtime across 3 overnight periods in a randomized order. Adverse events were collected by telephone contact with participants during each washout period. The primary endpoint was change in hypoxic burden and secondary endpoint was apnea-hypopnea index.RESULTSPatients treated with both the high and low doses of AD109 had a statistically significant and clinically meaningful difference from placebo in hypoxic burden. Median [interquartile range] hypoxic burden for participants on placebo was 13.9[4.5-21.9] (%min)/h vs 2.3[0.1-10.5] (%min)/h for patients on the high dose (P < .001) and to 7.3[2-12.5] (%min)/h on the low dose (P < .01). Apnea-hypopnea index went from a median of 13.2[8.0-19.1] events/h on placebo reduced to 5.5[2.2 to 9.6] events/h on the high dose (P < .001) and to 7.8[4-13.7] events/h on the low dose (P < .05). AD109 demonstrated a favorable safety profile.CONCLUSIONSThis study provides additional support that a pharmacological intervention for obstructive sleep apnea, namely the combination of atomoxetine and aroxybutynin, offers promising results. Additional development of this compound and others is warranted.CLINICAL TRIAL REGISTRATIONRegistry: ClinicalTrials.gov; Name: AD109 Dose Finding in Mild to Moderate OSA; URL: https://clinicaltrials.gov/ct2/show/NCT04631107; Identifier: NCT04631107.CITATIONRosenberg R, Abaluck B, Thein S. Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA. J Clin Sleep Med. 2022;18(12):2837-2844.

项与 Aroxybutynin/Atomoxetine 相关的新闻（医药）

2025-04-25

·shionogi.com

Shionogi Announces Further Agreement with Apnimed for Sleep Disorder Treatments - Introduction of New Assets to Joint Venture Shionogi-Apnimed Sleep Science – (SASS)

OSAKA, Japan, April 25, 2025 - Shionogi & Co., Ltd. (Head Office: Osaka, Japan; Chief Executive Officer: Isao Teshirogi, Ph.D.; hereafter "Shionogi") announced that it has entered into an agreement with Apnimed, Inc. (Head Office: Massachusetts, USA; Chief Executive Officer: Lawrence G. Miller, MD; hereafter "Apnimed") for the introduction of sulthiame* and a new drug development program. * Sulthiame: A carbonic anhydrase inhibitor approved as an antiepileptic drug in certain regions. Sulthiame has successfully completed two Phase 2 trials in over 300 obstructive sleep apnea (OSA) patients studied for up to 3 months in Europe.1 With the conclusion of this agreement, Shionogi acquired a joint ownership interest in the intellectual property rights related to the use of sulthiame in the field of sleep apnea and also in other intellectual property rights related to a different drug development program of Apnimed by paying a one-time fee to Apnimed.※ Furthermore, Shionogi and Apnimed have already equally contributed this intellectual property to SASS, which will now conduct thefuture research and development of sulthiame and the other drug development program. ※ Note: Shionogi retains exclusive negotiation rights for the development and sales rights in Japan, Korea, Taiwan, and China. “We are pleased to add new assets to the SASS OSA pipeline,” said John Keller, Ph.D., Senior Executive Officer, Senior Vice President, R&D Supervisory Unit at Shionogi. “Our joint venture, combining the scientific and medical resources of Apnimed and Shionogi, represents the most robust global effort to bring new pharmacologic treatments for people with sleep apnea and related disorders.” “We are delighted to announce that this transaction further strengthened our SASS pipeline,” commented Larry Miller, MD, Chief Executive Officer of Apnimed. “The 80 million people with OSA in the US, and hundreds of millions more around the globe, need more convenient options that directly treat the root causes of OSA.” Shionogi has identified Contributing to a Healthy and Prosperous Life as one of our material focus area. We are committed to creating a society where everyone can lead a longer, more vibrant life, realizing their goals. Through the partnership with Apnimed, Shionogi continues to strive to deliver innovative treatments for diseases with high unmet medical needs, including sleep apnea and related disorders, to patients as quickly as possible. About Apnimed Apnimed, based in Cambridge, Massachusetts, is a pharmaceutical company with exceptional expertise in sleep disorders. The company is building a portfolio of novel drug treatments for sleep-related breathing disorders, including Sleep Apnea Syndrome (SAS). Apnimed's lead development candidate, AD109, aims to maintain upper airway patency during sleep with a once-daily oral medication for the treatment of OSA, which, if approved, could bring a dramatic change to conventional therapies for OSA. For more details, please visit apnimed.com, X, or LinkedIn. About Shionogi-Apnimed Sleep Science, LLC In November 2023, Shionogi and Apnimed established a joint venture, Shionogi-Apnimed Sleep Science, LLC, with each company holding a 50% stake. 2 The aim of SASS is to provide promising solutions to meet the unmet needs in the field of sleep disorders. SASS combines Shionogi's capabilities in small molecule drug discovery, first-in-class and best-in-class compound creation with Apnimed's advanced expertise in the field of sleep disorders, including a highly experienced clinical-stage drug development team and a strong network with clinical facilities. This collaboration leverages superior translational research to create promising solutions in the field of sleep disorders more rapidly than either company could achieve alone. References: 1. Hedner et al. Efficacy, Safety, and Tolerability of Three Doses of Sulthiame in Patients With Obstructive Sleep Apnea. A Randomized, Double-blind, Placebo Controlled, Dose-ranging Study (STM-042/K). B14. American Thoracic Society Annual Meeting 2024. 2. Press Release: November 1, 2023 - Establishment of a Joint Venture Company with Apnimed for Solving Challenges in Sleep Disorders Forward-Looking Statements This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, lack of availability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise. For Further Information, Contact: SHIONOGI Website Inquiry Form: https://www.shionogi.com/global/en/contact.html

临床2期引进/卖出上市批准

2025-04-17

·CPHI制药在线

中药新药大爆发，宝仁堂药业进军“鼾症”市场

关注并星标CPHI制药在线4月9日，CDE官网显示，宝仁堂药业自主研发的1.1类创新中药“三贝苎鼾胶囊”的上市申请获受理。三贝苎鼾胶囊是宝仁堂药业依据祖传治疗“鼾症”的配方进行自主研发的中药，用于治疗阻塞性睡眠呼吸暂停（OSA）。2024年12月，该药治疗阻塞性睡眠呼吸暂停低通气综合征（痰瘀互结证）的多中心、随机、双盲、安慰剂平行对照3期临床试验总结会成功召开。结果显示：三贝苎鼾胶囊治疗OSA疗效显著，可明显降低呼吸暂停低通气指数（AHI），提高应答率，且药物安全性良好。OSA指患者在睡眠过程中反复出现呼吸暂停和低通气，临床表现为打鼾，鼾声大且不规律，夜间窒息感或憋醒，睡眠紊乱，白天出现嗜睡，记忆力下降，严重者出现认知功能下降，行为异常。据美国睡眠医学会估计，2025年全球OSA患病人数将增加到11.6亿。我国的OSA患者人数居全球首位，其次是美国、巴西和印度。目前，OSA的治疗手段主要包括危险因素控制（如饮食控制、加强锻炼）、体位治疗（无创气道正压通气治疗）、口腔矫治和外科手术治疗。2024年12月，FDA批准首款OSA直接治疗药物Zepbound（tirzepatide）。该药是全球首款获批上市的GLP-1/GIP双重受体激动剂，被FDA批准用于治疗中重度OSA合并肥胖症成人患者，且还被批准用于降糖和减重。此外，目前全球还有多款在研OSA新药，如AD109（Apnimed，3期临床）、IHL-42X（Incannex，2/3期临床）、THX-110（SciSparc，2期临床）、BIOS-0618（百诚医药，获批临床）。AD109是一种包含具选择性的去甲肾上腺素再摄取抑制剂托莫西汀与抗毒蕈碱aroxybutynin的组合配方，通过靶向OSA关键的神经通路，活化上呼吸道扩张肌，使得患者在睡眠时仍可维持呼吸道的畅通。AD109治疗OSA的2b期临床试验MARIPOSA结果显示：与安慰剂相比，AD109组患者的呼吸暂停低通气指数（AHI4，呼吸不足定义为4%饱和度降低）降低45%，达到主要研究终点。而且，2.5/75 mg AD109组患者在PROMIS疲劳量表（该量表测量日间疲劳程度及OSA对日常活动的影响）上表现出统计学显著改善。AD109使用方便，每天仅需睡前口服一次，曾被FDA授予快速通道资格。IHL-42X是屈大麻酚和乙酰唑胺的组合，已完成2期概念验证临床试验结果显示：与基线相比，使用低剂量 IHL-42X，患者AHI减少50.7%。此外，IHL-42X还能够改善患者的睡眠质量。THX-110是基于大麻素的创新药物之一，由屈大麻酚和大麻素棕榈酰乙醇酰胺组合而成。人的大脑和免疫系统中存在有大麻素受体，THX-110旨在刺激中枢神经系统的大麻素受体，抑制内源性大麻素的代谢降解，提高四氢大麻酚的吸收。中药新药大爆发2025第一季度批准8款在国家大力发展中医药创新的背景下，我国中药市场持续向好，中药创新也进一步加速。据悉2024年NMPA共批准12个中药新药，其中包括3个1.1类中药复方制剂（即儿茶上清丸、九味止咳口服液和秦威颗粒），8个3.1类按古代经典名方目录管理的中药复方制剂（即芍药甘草颗粒、苓桂术甘颗粒、温经汤颗粒、当归补血汤颗粒、二冬汤颗粒、一贯煎颗粒、枇杷清肺颗粒）和1个3.2类其他来源于古代经典名方的中药复方制剂（即温阳解毒颗粒）。2025年中药新药获批数量有望再攀新高。据悉，2025年第一季度NMPA已批准8款中药新药（详见下表），其中包括2款1.1类中药复方制剂。此外，截至2025年4月10日，据CDE官网，已有17款中药新药申请上市（详见下图），其中包括4款1.1类新药，即宝仁堂药业的三贝苎鼾胶囊（治疗阻塞性睡眠呼吸暂停）、以岭药业的芪桂络痹通片（治疗类风湿关节炎）、康缘药业的六味地黄苷糖片（治疗更年期综合征）和天士力的安神滴丸（治疗失眠症）。仅从2025年第一季度批准以及报产的中药新药来看，我国中药新药进入收获期，且覆盖的适应症愈发广泛。期待在利好政策的加持下，我国中药新药在人类抗击疾病的历史上更佳灿烂辉煌。END2025金笔奖征文即将截止，速来投稿！领取CPHI & PMEC China 2025展会门票智药研习社课程预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

快速通道临床3期临床2期临床结果上市批准

2025-04-07

·PRNewswire

Apnimed Provides Clinical Updates for Multiple Product Candidates

First Patient Dosed in Phase 2A Dose-Finding, Proof-of-Concept RESTEADY Trial Evaluating SASS-001 in a Sub-Population of Patients with Sleep Apnea with a Central Component; Top-line Data Expected in 1H 2026 SASS-001, a Novel Drug Combination of Sivopixant and a second compound, is the first clinical stage asset from Apnimed's Joint Venture with Shionogi Both Phase 3 Trials (SynAIRgy and LunAIRo) evaluating AD109 in Mild, Moderate and Severe Obstructive Sleep Apnea (OSA) patients of all body types remain on track for top-line results expected in Q2 and Q3 2025, respectively CAMBRIDGE, Mass., April 7, 2025 /PRNewswire/ -- Apnimed, Inc., a pharmaceutical company building the industry-leading portfolio of first-in-class oral drug candidates that address the root causes of obstructive sleep apnea (OSA) and other sleep-related breathing diseases, today announced that the first patient has been dosed in the Phase 2A RESTEADY trial evaluating the novel oral drug combination, SASS-001, in an underserved population of patients suffering from sleep apnea with a central component. Top-line results from the study are expected in the first half of 2026. SASS-001 represents the first clinical stage asset from Shionogi-Apnimed Sleep Science, LLC (SASS), Apnimed's joint venture with Shionogi & Co., Ltd. (Shionogi). "With the first patient dosed in the Phase 2A RESTEADY trial, both Apnimed and SASS have reached an important milestone – the advancement of a scientific hypothesis to clinical development," commented Larry Miller, MD, Chief Executive Officer of Apnimed. "Today's announcement represents the combined efforts of the Apnimed and Shionogi teams, highlighting their respective strengths in sleep medicine drug development and drug discovery." RESTEADY is a Phase 2A, multicenter, double-blind randomized, controlled, dose escalation, parallel-arm, safety and efficacy study evaluating SASS-001 in adult patients suffering from sleep apnea with a central component (NCT06776432). The study is expected to enroll approximately 60 patients from up to 10 U.S. clinical sites. Patients will be randomized in a 3:1 ratio to either dose-escalating SASS-001 or a placebo arm. Patient participation in the study is approximately 10 weeks, with trial measures to include sleep-clinic polysomnography and at-home sleep evaluations. Apnimed's most advanced clinical program, AD109, also continues to progress following the conclusion of enrollment in both Phase 3 clinical trials, LunAIRo and SynAIRgy. The Company continues to anticipate the availability of top-line data from both trials in Q2 and Q3 2025, respectively. AD109 is being studied in obese and non-obese adult patients with mild, moderate and severe OSA. About SASS and SASS-001 SASS is a joint venture of Apnimed and Shionogi focused on accelerating the discovery, preclinical and clinical development of novel pharmacologic solutions designed to address the complex pathology of sleep apnea and other sleep related diseases. SASS-001 is an investigational oral clinical candidate under development by SASS for sleep apnea with a central component. The candidate is a combination of sivopixant, a selective P2X3 receptor antagonist, and a second compound. About Sleep Apnea with a Central Component Sleep apnea with a central component is characterized by the concomitant presence of obstructive and central apneas. In central apneas, breathing temporarily stops due to absence of the signal from the nervous system to respiratory muscles to initiate a breath. This mechanism is different from the neuromuscular dysfunction that is thought to cause OSA, in which a breath is initiated but airflow is prevented by a physical occlusion of the airway despite contraction of respiratory muscles. Central and obstructive apneas often coexist in an individual patient, particularly in those with concomitant cardiovascular diseases such as atrial fibrillation and heart failure. About Obstructive Sleep Apnea Obstructive sleep apnea (OSA) is a serious, chronic sleep-related breathing disease in which the upper airway repeatedly collapses during sleep, leading to intermittent oxygen deprivation. It is caused by two overlapping mechanisms: neuromuscular dysfunction during sleep and predisposing anatomic abnormalities. It has been demonstrated that OSA affects people of all body types, ages and genders —there is no single "face" of the disease. An estimated 80 million people in the United States and 1 billion people worldwide suffer from OSA. An individual with OSA can experience hundreds of sleep apnea events in a single night, each one reducing the blood oxygen levels and negatively impacting cellular functions vital to normal health and function. Failure to effectively treat OSA increases the risk of serious long-term health consequences, such as high blood pressure, cardiovascular disease and type 2 diabetes, along with impacts on quality of life, including daytime fatigue and impaired judgement. Yet, the majority of those diagnosed with OSA refuse, abandon, or underutilize treatment. Currently, no available pharmacological treatments directly address the underlying neuromuscular dysfunction that is present in all people with OSA. About Apnimed Apnimed is a privately held clinical-stage pharmaceutical company dedicated to transforming the treatment landscape for sleep-related breathing diseases. We believe the introduction of simple, once-nightly oral drugs will dramatically expand diagnosis and the reach of treatment for people with OSA. OSA, like other common chronic diseases such as diabetes or hypertension, would benefit from having multiple drugs with differing mechanisms to more fully address the heterogeneity of disease pathophysiology. Apnimed envisions a new era where novel oral therapies simplify intervention, expand the reach of diagnosis and treatment, and help more people get the oxygen and restorative sleep needed to thrive. Based in Cambridge, Mass., Apnimed is advancing its growing pipeline of oral pharmaceutical product candidates designed to improve oxygenation in individuals living with OSA and other sleep-related breathing disorders. Our lead candidate AD109 could become the catalyst for a new oral treatment paradigm for OSA that has been historically limited to cumbersome devices or invasive surgeries. AD109 is currently in two Phase 3 clinical trials for the treatment of mild, moderate and severe OSA. Apnimed is developing several therapies through our joint venture with Shionogi & Co., Ltd., Shionogi Apnimed Sleep Science. Learn more at apnimed.com or follow us on X and LinkedIn. Media Contact: [email protected] Investor Contact: Ramzi Benamar [email protected] SOURCE Apnimed, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期临床3期

100 项与 Aroxybutynin/Atomoxetine 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
阻塞性睡眠呼吸暂停综合征	临床3期	美国	Apnimed, Inc.	2023-08-28

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04580394 (CTgov)	临床2期	阻塞性睡眠呼吸暂停综合征	60	Digit System Substitution Test+AD109 (AD109)	鏇膚醖網憲壓窪憲築範(顧淵鏇蓋醖繭願壓鏇繭) = 膚製築製醖鬱簾窪襯鬱艱夢鑰膚糧鏇範廠構遞 (窪鏇繭獵顧艱廠醖廠遞, 範夢憲衊鏇淵蓋夢網選 ~ 構壓鑰衊壓築鑰鏇遞襯)	-	2023-01-31
				Digit System Substitution Test+Atomoxetine (Atomoxetine)	鏇膚醖網憲壓窪憲築範(顧淵鏇蓋醖繭願壓鏇繭) = 鬱築壓繭顧衊糧餘淵鏇艱夢鑰膚糧鏇範廠構遞 (窪鏇繭獵顧艱廠醖廠遞, 壓膚鹹淵廠範遞鑰膚鏇 ~ 繭鹽範膚齋糧鏇遞顧製)
NCT04631107 (CTgov)	临床2期	阻塞性睡眠呼吸暂停综合征	32	Placebo+AD109 (AD109 dose1 vs Placebo)	醖鹹願醖顧窪膚網構繭(淵積艱繭觸範積餘選繭) = 襯醖窪遞廠構鹽襯簾醖鹽範齋夢網繭襯網鑰構 (願繭膚觸網膚衊艱憲構, 蓋範淵遞獵糧願廠選鏇 ~ 鹹鹽鑰廠餘衊夢鏇淵簾) 更多	-	2022-12-22
				Placebo+AD109 (AD109 dose2 vs Placebo)	醖鹹願醖顧窪膚網構繭(淵積艱繭觸範積餘選繭) = 鏇觸衊淵簾淵餘襯鹹艱鹽範齋夢網繭襯網鑰構 (願繭膚觸網膚衊艱憲構, 鹽膚壓範壓選襯簾構窪 ~ 構築廠選網蓋鏇襯壓構) 更多