A multiple dose, dose-finding, placebo controlled, double blind, randomized trial to compare the effect of treatment on plaque burden as determined by intravascular ultrasound and evaluate the efficacy, safety, and tolerability of MDCO-216 given as multiple weekly infusions in subjects with a recent acute coronary syndrome event - MILANO DRIVE

开始日期2016-10-26

申办/合作机构

The Medicines Co.

EUCTR2015-000826-13-CZ / Not yet recruiting临床2期

A placebo-controlled, double-blind, randomized trial to compare the effect of treatment on plaque burden as determined by intravascular ultrasound and to evaluate the efficacy, pharmacokinetics, safety, and tolerability of MDCO-216 given as multiple weekly infusions in subjects with a recent acute coronary syndrome. - MILANO PILOT

开始日期2016-01-20

申办/合作机构

The Medicines Co.

NCT02678923 / Completed临床1/2期

A Placebo-controlled, Double-blind, Randomized Trial to Compare the Effect of Treatment on Plaque Burden as Determined by Intravascular Ultrasound and to Evaluate the Efficacy, Pharmacokinetics, Safety, and Tolerability of MDCO-216 Given as Multiple Weekly Infusions in Subjects With a Recent Acute Coronary Syndrome

This study will be a proof-of-concept, placebo-controlled, double-blind, randomized trial in participants with a recent acute coronary syndrome (ACS) to evaluate the efficacy, pharmacokinetics, safety, tolerability, disease progression measures by IVUS, and pharmacodynamics of MDCO-216 infusion. Eligible participants will be randomized to receive 5 infusions of MDCO-216 20 milligrams/kilogram (mg/kg) or placebo in a 1:1 ratio.

开始日期2015-12-03

申办/合作机构

The Medicines Co.

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100 项与 MDCO-216 相关的临床结果

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100 项与 MDCO-216 相关的转化医学

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100 项与 MDCO-216 相关的专利（医药）

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项与 MDCO-216 相关的文献（医药）

2023-08-01·British journal of pharmacology

Therapeutic effect of human ApoA‐I‐Milano variant in aged transgenic mouse model of Alzheimer's disease

Article

作者: Bonaterra-Pastra, Anna ; Castellote, Laura ; Giménez-Llort, Lydia ; Solé, Montse ; Marazuela, Paula ; Hernández-Guillamon, Mar

Background and Purpose:

Therapies based on apolipoprotein A‐I (ApoA‐I), classically tested for cardiovascular diseases, were recently proposed for Alzheimer's disease (AD). Based on a drug reprofiling approach, our objective was to explore the use of a natural variant of ApoA‐I form, ApoA‐I‐Milano (M), as a treatment for AD. ApoA‐I‐M contains the R173C mutation, and confers protection against atherosclerosis development, although ApoA‐I‐M carriers exhibit low HDL levels.

Experimental Approach:

Middle‐aged (12‐month‐old) and aged (21‐month‐old) APP23 mice were intraperitoneally treated for 10 weeks with human recombinant ApoA‐I‐M (hrApoA‐I‐M) protein or saline. Pathology progression through behavioural parameters and biochemical determinations was evaluated.

Key Results:

In middle‐aged group, hrApoA‐I‐M treatment reduced the anxiety behaviour associated with this AD model. In aged mice, hrApoA‐I‐M reversed T‐Maze performance alterations, a cognitive improvement accompanied by neuronal loss recovery in the dentate gyrus. Aged mice treated with hrApoA‐I‐M showed lower brain Aβ40 soluble levels and elevated Aβ40 levels in cerebrospinal fluid, without modifying insoluble brain Aβ burden. Interestingly, hrApoA‐I‐M sub‐chronic treatment induced a molecular effect on the cerebrovasculature, increasing occludin expression and ICAM‐1 presence, as well as promoting an elevation of plasma soluble RAGE in all hrApoA‐I‐M‐treated mice, drastically decreasing the AGEs/sRAGE ratio, a marker of endothelial damage.

Conclusion and Implications:

Peripheral hrApoA‐I‐M treatment shows a beneficial impact on working memory, involving mechanisms related with brain Aβ mobilization and modulation of the levels of cerebrovascular markers. Our study shows the potential therapeutic applicability of a safe and non‐invasive treatment based on peripheral administration of hrApoA‐I‐M in AD.

2022-07-01·Current Atherosclerosis Reports2区 · 医学

ApoA-I Infusion Therapies Following Acute Coronary Syndrome: Past, Present, and Future

2区 · 医学

Review

作者: Libby, Peter ; Shaunik, Alka ; Fitzgerald, Clara ; Korjian, Serge ; Kalayci, Arzu ; Duffy, Danielle ; Tricoci, Pierluigi ; Lee, Jane J ; Gibson, C Michael ; Wright, Samuel D ; Chi, Gerald ; Kazmi, S Hassan ; Berman, Gail ; Kingwell, Bronwyn A ; Ridker, Paul M

Purpose of Review:

The elevated adverse cardiovascular event rate among patients with low high-density lipoprotein cholesterol (HDL-C) formed the basis for the hypothesis that elevating HDL-C would reduce those events. Attempts to raise endogenous HDL-C levels, however, have consistently failed to show improvements in cardiovascular outcomes. However, steady-state HDL-C concentration does not reflect the function of this complex family of particles. Indeed, HDL functions correlate only weakly with serum HDL-C concentration. Thus, the field has pivoted from simply raising the quantity of HDL-C to a focus on improving the putative anti-atherosclerotic functions of HDL particles. Such functions include the ability of HDL to promote the efflux of cholesterol from cholesterol-laden macrophages. Apolipoprotein A-I (apoA-I), the signature apoprotein of HDL, may facilitate the removal of cholesterol from atherosclerotic plaque, reduce the lesional lipid content and might thus stabilize vulnerable plaques, thereby reducing the risk of cardiac events. Infusion of preparations of apoA-I may improve cholesterol efflux capacity (CEC). This review summarizes the development of apoA-I therapies, compares their structural and functional properties and discusses the findings of previous studies including their limitations, and how CSL112, currently being tested in a phase III trial, may overcome these challenges.

Recent Findings:

Three major ApoA-I-based approaches (MDCO-216, CER-001, and CSL111/CSL112) have aimed to enhance reverse cholesterol transport. These three therapies differ considerably in both lipid and protein composition. MDCO-216 contains recombinant ApoA-I Milano, CER-001 contains recombinant wild-type human ApoA-I, and CSL111/CSL112 contains native ApoA-I isolated from human plasma. Two of the three agents studied to date (apoA-1 Milano and CER-001) have undergone evaluation by intravascular ultrasound imaging, a technique that gauges lesion volume well but does not assess other important variables that may relate to clinical outcomes. ApoA-1 Milano and CER-001 reduce lecithin-cholesterol acyltransferase (LCAT) activity, potentially impairing the function of HDL in reverse cholesterol transport. Furthermore, apoA-I Milano can compete with and alter the function of the recipient’s endogenous apoA-I. In contrast to these agents, CSL112, a particle formulated using human plasma apoA-I and phosphatidylcholine, increases LCAT activity and does not lead to the malfunction of endogenous apoA-I. CSL112 robustly increases cholesterol efflux, promotes reverse cholesterol transport, and now is being tested in a phase III clinical trial.

Summary:

Phase II-b studies of MDCO-216 and CER-001 failed to produce a significant reduction in coronary plaque volume as assessed by IVUS. However, the investigation to determine whether the direct infusion of a reconstituted apoA-I reduces post-myocardial infarction coronary events is being tested using CSL112, which is dosed at a higher level than MDCO-216 and CER-001 and has more favorable pharmacodynamics.

2022-05-01·Bioresource technology1区 · 工程技术

Direct processing of alginate-immobilized microalgae into polyhydroxybutyrate using marine bacterium of Saccharophagus degradans

1区 · 工程技术

Article

作者: Huo, Shuhao ; Stratton, Jayne ; Meneses, Yulie E ; Hu, Xinjuan

Alginate immobilized microalgae (AIM) was found efficient in algal cells separation and pollutants removal, however, its processing required alginate removal. In present study, polysaccharide-degrading bacterium of Saccharophagus degradans was used to biodegrade alginate and microalgae in AIM and produce polyhydroxybutyrate (PHB). Results showed that AIM cultivated in wastewater contained 34.0% carbohydrate and 45.7% protein. S. degradans effectively degraded and utilized polysaccharide of AIM to maintain five-day continuous growth at 7.1-8.8 log CFU/mL. Compared with glucose, S. degradans metabolism of mixed polysaccharide in AIM maintained the medium pH at 7.1-7.8. Increasing the inoculum concentration did not enhance AIM utilization by S. degradans due to the carbon catabolite repression of glucose which likely inactivated hydrolysis enzymes. PHB production in S. degradans peaked at 64.9 mg/L after 72 h cultivation but was later degraded to provide energy. Conclusively, S. degradans was effective in direct processing of AIM while showing potential in PHB production.

项与 MDCO-216 相关的新闻（医药）

2023-05-30

·Medical Design and Outsourcing

Brain-spine ‘digital bridge’ allows spinal cord injury patient to walk — and enjoy a beer

A wireless “digital bridge” between a paralyzed patient’s brain and spinal cord has allowed him to walk naturally, researchers say. The experimental technology uses electronic implants on the brain and spinal cord to relay leg movement control signals, allowing 40-year-old Gert-Jan Oksam to walk again 12 years after a bicycle accident. Neuroscientists and neurosurgeons from Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne University Hospital (CHUV) and University of Lausanne (UNIL) published their research in Nature last week. “We have implanted Wimagine devices above the region of the brain that is responsible for controlling leg movements,” neurosurgeon Jocelyne Bloch explained in a news release. “These devices … decode the electrical signals generated by the brain when we think about walking. We also positioned a neurostimulator connected to an electrode array over the region of the spinal cord that controls leg movement.” Bloch and Grégoire Courtine, a neuroscience professor at EPFL, CHUV and UNIL, led the project through NeuroRestore, a EPFL and CHUV research and innovation center focused on restoring neurological functions through medical therapies. Previously: Paralyzed patients walk, swim and cycle with spinal cord neuromodulation implant Implants and algorithms made ‘digital bridge’ possible Developed by the French Alternative Energies and Atomic Energy Commission (CEA), the implantable Wimagine brain device previously allowed a tetraplegic patient to control an exoskeleton . “Thanks to algorithms based on adaptive artificial intelligence methods, movement intentions are decoded in real-time from brain recordings,” said Guillaume Charvet, head of the brain-computer interface (BCI) program at CEA. The new system converts movement intentions from the brain into electrical stimulation sequences on the spinal cord to activate leg muscles as desired. This wireless digital bridge from the brain to electrodes placed on the part of the spinal cord that controls leg movements bypasses the injured part of the spinal cord. Oksam can now stand, walk, climb stairs — and enjoy a beer with friends at a bar while on his own two feet. “This simple pleasure represents a significant change in my life,” Oksam said in the news release. After the surgeries to implant the devices in the brain and on the spine, Oksam needed to learn how to use his legs again, but said it was a faster process than he expected. “The most surprising thing I think happened after two days,” Oksam said in the video below. “Within five to ten minutes, I could control my hips — the brain implant picked up what I was doing with my hips.” The researchers said they could measure “remarkable improvements” in Oksam’s sensory perceptions and motor skills even when the digital bridge was turned off, suggesting new nerve connections may have developed. Onward: The next steps Oksam is the first and only patient to “test pilot” the technology so far. But the researchers said the digital bridge approach between brain and spine could be used to restore arm and hand movements for spinal cord injury patients, or to treat paralysis due to stroke. The European Commission’s European Innovation Council is supporting commercial development of the technology through CEA, EPFL and medtech developer Onward Medical. Led by former Medtronic executive Dave Marver as CEO, Onward Medical makes external and implantable stimulation systems, including the implantable ARC-IM lead used in Oksam’s therapy. The company designed ARC-IM specifically to help spinal cord injury (SCI) patients regain movement and function. “This publication shows the remarkable potential of ARC Therapy to be enhanced with the introduction of a BCI, facilitating more natural movement based on the thoughts of a person living with paralysis,” Marver said about the research project. “We have positioned Onward as a leader in the BCI field with our unique understanding of spinal cord stimulation for people with SCI.” Onward Medical is headquartered in the Netherlands and said it also has a growing U.S. team in Boston. The company has won nine FDA breakthrough device designations. The most recent was for its ARC-IM therapy for spasticity in people with SCI. Onward is also exploring ARC-IM for improved blood pressure management, mobility, upper extremity function, and bladder control. Onward expects to start commercializing its products with the launch of its external ARC-EX as soon as this year or early next year, pending FDA de novo clearance for an upper limb indication.

突破性疗法

2023-05-24

·Mass Device

Research supports brain-computer interface tech from Onward

The data, published in Nature, demonstrates how the BCI uses thought to modulate ARC therapy. Researchers say that, when paired with ARC therapy, an implanted BCI allowed an individual to gain augmented control over when and how he moved his paralyzed legs. Onward designed its ARC-IM lead to restore movement, function and independence in people with spinal cord injury (SCI). The Eindhoven, the Netherlands-based company developed ARC-IM to deliver targeted electrical pulses to the spinal cord. It represents a key component of the Onward ARC-IM system engineered to deliver ARC therapy to address multiple indications. The company completed first-in-human use for its movement-restoring lead earlier this month. “This publication shows the remarkable potential of ARC Therapy to be enhanced with the introduction of a BCI, facilitating more natural movement based on the thoughts of a person living with paralysis,” said Dave Marver, CEO of Onward. “We have positioned Onward as a leader in the BCI field with our unique understanding of spinal cord stimulation for people with SCI.” Onward said the data comes as part of an ongoing clinical feasibility study. It investigates the safety and preliminary effectiveness of brain-controlled spinal cord stimulation after SCI. All Onward devices and therapies remain investigational and unavailable for commercial use at this time. “The BCI establishes a continuous link between movement intentions and spinal cord stimulation, allowing for more natural restoration of mobility,” said neuroscientist Grégoire Courtine, professor at EPFL and co-author of the Nature paper. “I look forward to working with the ONWARD team to advance this important new technology.”

2023-05-16

·BioSpace

ONWARD Reports Q1 Business Update and Year-To-Date Highlights

First-in-Human Use of the ARC-IM™ Lead New Breakthrough Device Designation Awarded by the U.S. FDA for ARC Therapy™, Bringing Total to 9 10 Additional Patents Issued, Bringing Total Pending and Issued Patents to More than 340 and Strengthening First-Mover Advantage EINDHOVEN, the Netherlands, May 16, 2023 (GLOBE NEWSWIRE) -- ONWARD Medical N.V. (Euronext: ONWD), the medical technology company creating innovative therapies to restore movement, function, and independence in people with spinal cord injury (SCI), today provided a first quarter 2023 business update. “Our team continued to execute at a high level in Q1, achieving milestones and adding strength across our range of activities,” said Dave Marver, CEO of ONWARD. “We were especially pleased to announce that the Up-LIFT pivotal study met all primary endpoints including a 72% responder rate. We expect to achieve several important milestones in the months ahead, including FDA submission of our de novo application for ARC-EX® Therapy and initiation of a groundbreaking clinical feasibility study that includes first-in-human use of a brain-computer interface in combination with ARC-IM™ Therapy to restore hand and arm function.” Q1 and Year-To-Date Highlights: Clinical and Development The Company has been issued 10 new patents during Q1 2023, bringing the total number of issued or pending patents to more than 340 and strengthening its first-mover advantage. In April 2023 at the American Academy of Neurology Annual Meeting, Dr. James Guest, Professor of Neurological Surgery at the University of Miami and the Miami Project to Cure Paralysis, shared detailed results from the Up-LIFT pivotal study that investigated non-invasive neuromodulation for improving upper extremity strength and function after SCI. In addition to meeting all primary safety and effectiveness endpoints, the study demonstrated that 72% of participants responded1 to ARC-EX Therapy. The Company has been awarded Breakthrough Device Designation (BDD) for ARC-IM Therapy for spasticity in people with SCI. Breakthrough Device Designation is an FDA program aimed at helping patients and their clinicians receive timely access to new treatments. The Company now has a total of 9 BDDs, which affords it priority FDA review and the opportunity to interact with FDA experts throughout the pre-market review phase as the technology moves toward commercialization. First-in-human use of the Company’s ARC-IM Lead, which was used with the investigational implantable ARC-IM system as part of the ongoing HemON study to evaluate use of ARC-IM Therapy to better regulate blood pressure after SCI. ONWARD is developing a portfolio of ARC-IM Leads in a range of sizes, shapes, and electrode arrays for the many indications the Company is developing or exploring, such as improved blood pressure management, mobility, upper extremity function, and bladder control. The ARC-IM Lead was specifically designed to stimulate the spinal cord anatomy to restore movement and function in people with SCI. Corporate and Financial The Company reported cash and cash equivalents of EUR 53 million as of March 31, 2023 and reiterated its guidance of expected cash runway through the end of 2024. In Q1 2023, ONWARD strengthened its leadership team, appointing Erika Ross Ellison as Vice President, Global Clinical & Regulatory, and Sarah Moore as Vice President, Global Marketing. Erika comes to ONWARD from Abbott Neuromodulation, where she was Director, Global Clinical & Applied Research. She also served as Deputy Director, Medical Device Innovation Accelerator, Department of Surgery and Assistant Professor, Department of Neurologic Surgery at Mayo Clinic. Sarah comes to ONWARD from Nevro, an implantable neuromodulation company, and has more than 20 years of experience in new product development and commercial marketing in medical devices, including at Johnson & Johnson. Outlook: ONWARD expects to continue steady and consistent execution of its strategy in 2023 and beyond with the achievement of the following milestones: The Company plans to submit a de novo application for FDA clearance for the ARC-EX system this year and aims to submit an application for European authorization in the same period. The Company also plans to begin its pivotal clinical study in the next year to evaluate the safety and effectiveness of the implantable ARC-IM system to better regulate blood pressure after SCI. The Company plans to begin clinical feasibility studies to investigate the ability for a brain-computer interface (BCI) to communicate with the ARC-IM system to enable a person with SCI to more naturally control when and how they move. This program is supported by a grant from the European Innovation Council. The Company plans to continue to build organizational capabilities in preparation for expected launch of ARC-EX later this year or early next year, recruiting field sales and service professionals and adding operational systems that will enable it to conduct commerce once it receives FDA clearance and CE mark. The Company anticipates its current cash position will fuel operations through the end of 2024. In 2023, it plans to pursue opportunities to further strengthen cash position to support future investments in product development, clinical trials, and operational and commercial capabilities. Conference Call & Webcast ONWARD will host a conference call with a live webcast today, May 16, 2023, at 2:00 pm CET / 8:00am ET. The webcast may be accessed on the Financial Information page of the Company’s website. A replay of the webcast also will be available on the ONWARD website. To join the webcast via Zoom, please register using this link. All ONWARD devices and therapies referenced here, including but not limited to ARC-IM, ARC-EX, and ARC Therapy, are investigational and not available for commercial use. 1Responder was defined as a participant who met or exceeded the minimally important difference criteria for at least one outcome of the strength domain and at least one outcome of the functional performance domain. About ONWARD® Medical ONWARD is a medical technology company creating innovative therapies to restore movement, function, and independence in people with spinal cord injuries. The Company’s work builds on more than a decade of basic science and preclinical research conducted at the world’s leading neuroscience laboratories. ONWARD ARC Therapy™, which can be delivered by implantable (ARC-IM™) or external (ARC-EX®) systems, is designed to deliver targeted, programmed spinal cord stimulation to restore movement and other functions in people with spinal cord injury, ultimately improving their quality of life. ONWARD has received nine Breakthrough Device Designations from the U.S. FDA. ARC-EX is an external, non-invasive platform consisting of a stimulator and wireless programmer. Positive top-line data were reported in 2022 from the Company’s first pivotal study, called Up-LIFT, evaluating the ability of transcutaneous ARC Therapy to improve upper extremity strength and function. The Company is now preparing marketing approval submissions for the US and Europe. ARC-IM consists of an implantable pulse generator and lead placed near the spinal cord. The Company completed the first-in-human use of the ARC-IM neurostimulator and reported positive interim clinical outcomes for ARC-IM Therapy for improved blood pressure regulation following SCI in 2022. ONWARD is headquartered in Eindhoven, the Netherlands. It maintains a Science and Engineering Center in Lausanne, Switzerland, and has a growing U.S. presence in Boston, Massachusetts. The Company has an academic partnership with .NeuroRestore, a collaboration between EPFL, the Swiss Federal Institute of Technology in Lausanne, and Lausanne University Hospital (CHUV). For additional information about the Company, please visit ONWD.com. To access our 2023 Financial Calendar, please visit IR.ONWD.com. For Company Enquiries: info@onwd.com For Media Enquiries: Aditi Roy, VP Communications media@onwd.com For Investor Enquiries: Lara Smith Weber, CFO investors@onwd.com Disclaimer Certain statements, beliefs, and opinions in this press release are forward-looking, which reflect the Company’s or, as appropriate, the Company directors’ current expectations and projections about future events. By their nature, forward-looking statements involve several risks, uncertainties, and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties, and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition, and technology, can cause actual events, performance, or results to differ significantly from any anticipated development. Forward-looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions, or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such person’s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

高管变更突破性疗法

100 项与 MDCO-216 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
动脉粥样硬化	临床2期	加拿大	The Medicines Co.	2015-12-03
动脉粥样硬化	临床2期	捷克	The Medicines Co.	2015-12-03
动脉粥样硬化	临床2期	匈牙利	The Medicines Co.	2015-12-03
动脉粥样硬化	临床2期	荷兰	The Medicines Co.	2015-12-03
动脉粥样硬化	临床2期	波兰	The Medicines Co.	2015-12-03
急性冠状动脉综合征	临床2期	美国	The Medicines Co.	-
急性冠状动脉综合征	临床2期	加拿大	The Medicines Co.	-
急性冠状动脉综合征	临床2期	捷克	The Medicines Co.	-
急性冠状动脉综合征	临床2期	匈牙利	The Medicines Co.	-
急性冠状动脉综合征	临床2期	荷兰	The Medicines Co.	-

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临床结果

适应症

分期

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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


NCT02678923 (MILANO-PILOT, Pubmed) 人工标引	临床1/2期	急性冠状动脉综合征 \| 冠状动脉疾病	122	MDCO-216	壓衊繭淵憲鹹憲鑰夢憲(簾窪衊網憲鏇餘淵壓鑰) = 繭廠醖鹽網鑰選夢積積鹹襯窪簾鏇顧艱夢憲製 (積選憲顧遞餘夢顧簾憲 ) 更多	不佳	2018-09-01
				Placebo	壓衊繭淵憲鹹憲鑰夢憲(簾窪衊網憲鏇餘淵壓鑰) = 餘鹹範鏇窪積壓鏇淵構鹹襯窪簾鏇顧艱夢憲製 (積選憲顧遞餘夢顧簾憲 ) 更多
NCT02678923 (MILANO-PILOT, CTgov)	临床1/2期	急性冠状动脉综合征 \| 动脉粥样硬化	126	MDCO-216 (MDCO-216)	壓鹹選鹽艱簾鏇衊壓憲(鑰夢鏇願廠網積壓膚廠) = 鹹觸憲夢壓齋糧齋簾構廠鹹醖鑰簾顧淵糧構獵 (窪網鏇鹽糧積艱繭夢鹽, 鹽獵獵鬱憲願簾願鹽範 ~ 願襯蓋蓋築淵積憲廠鏇) 更多	-	2017-07-13
				Placebo (Placebo)	壓鹹選鹽艱簾鏇衊壓憲(鑰夢鏇願廠網積壓膚廠) = 獵醖醖構鑰鏇遞簾顧製廠鹹醖鑰簾顧淵糧構獵 (窪網鏇鹽糧積艱繭夢鹽, 齋鹽蓋醖簾醖製積鑰齋 ~ 築遞觸膚餘夢鏇膚觸顧) 更多