This is a randomized, double-blind, placebo-controlled, multicenter study in participants with Parkinson's disease (PD) with motor fluctuations. Participants will be randomized to receive once-daily oral doses of either 75 milligrams (mg) CVN424, 150 mg CVN424, or a matching placebo for 12 weeks. Participants who successfully complete this study and retain eligibility/suitability will be invited to participate in a future open-label extension (OLE) study.

开始日期2024-09-20

申办/合作机构

Cerevance, Inc.初创企业

NCT06006247 / Active, not recruiting临床2期

A Randomized, Double-Blind, Placebo-Controlled Trial of CVN424 in Early Parkinson's Disease

This is a multicenter, 12-week, placebo-controlled clinical trial of CVN424 150 milligrams (mg) tablets in early, untreated Parkinson's Disease (PD). Participants will be randomized in a 1:1 ratio to CVN424 150 mg or placebo at the Baseline Visit. The purpose of this study is to measure effect on motor features with CVN424 tablets compared to placebo in early, untreated PD and to evaluate the potential of CVN424 to improve motor and non-motor functions in participants with early PD who are not taking dopaminergic or anti-PD therapies.

开始日期2023-09-11

申办/合作机构

Cerevance, Inc.初创企业

NCT05635461 / Completed临床1期

A Randomized, Open-Label, Single Oral Dose, Three-Way Cross-Over Trial to Evaluate the Relative Bioavailability of CVN424 Suspension &Tablet Formulations Including an Assessment of the Effect of Food on the Tablet Formulation in Healthy Adult Volunteers

This is a Randomized, Open-Label, Single Oral Dose, Three-Way Cross-Over Trial to Evaluate the Relative Bioavailability of CVN424 Suspension and Tablet Formulations in Healthy Volunteers Under Fasted and Fed Conditions.

开始日期2022-10-09

申办/合作机构

Cerevance, Inc.初创企业

100 项与 CVN-424 相关的临床结果

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100 项与 CVN-424 相关的转化医学

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100 项与 CVN-424 相关的专利（医药）

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项与 CVN-424 相关的文献（医药）

2024-11-01·eClinicalMedicine

CVN424, a GPR6 inverse agonist, for Parkinson's disease and motor fluctuations: a double-blind, randomized, phase 2 trial

Article

作者: Olanow, C Warren ; Ellenbogen, Aaron L ; Brice, Nicola L ; Kieburtz, Karl ; Dawson, Lee A ; Matthews, Kim L ; Carlton, Mark ; Bexon, Martin ; Dubow, Jordan ; Margolin, David H

BackgroundCVN424 is a GPR6 inverse agonist that provides selective pharmacological control of the indirect striatopallidal pathway. We assessed the safety and efficacy of CVN424 as an adjunctive treatment to levodopa for reducing OFF-time in individuals with Parkinson's disease (PD) experiencing motor-fluctuations.MethodsThis was a randomised, double-blind, placebo-controlled study conducted at 21 sites across the United States to evaluate two doses of CVN424 (NCT04191577). Patients with PD (Hoehn and Yahr stages 2-4) who were on a stable dose of levodopa and experiencing ≥2 h of daily OFF-time were randomised (1:1:1) to receive either once-daily CVN424 (50 mg or 150 mg) or placebo for a 28-day treatment period. The primary endpoints were safety and tolerability. The key secondary endpoint was the change from baseline to Day 27 in OFF-time.FindingsThe study was conducted from December 23, 2019, to October 14, 2021. Out of 198 participants screened, 141 eligible participants were randomised to one of the three treatment groups (n = 47 per group), and 127 participants completed the 28-day treatment period. The most common treatment emergent adverse events (TEAEs) were headache (2% with CVN424 50 mg, 9% with CVN424 150 mg, and 2% with placebo) and nausea (4% with CVN424 50 mg, 6% with CVN424 150 mg and 2% with placebo). No serious treatment-related adverse events were reported. On Day 27, the mean ± standard deviation (SD) change from baseline in daily OFF-time was -1.3 ± 3.0 h in the CVN424 50 mg group, -1.6 ± 2.5 h in the CVN424 150 mg group, and -0.5 ± 2.9 h in the placebo group. The placebo-adjusted LS mean ± standard error (SE) treatment difference was significant for the CVN424 150 mg dose (1.3 ± 0.56 h, [95 CI% -2.41 to -0.19], nominal p = 0.02).InterpretationTreatment with CVN424 was safe and well-tolerated. Despite the short study duration and small sample size, the 150 mg CVN424 dose provided a clinically meaningful reduction in daily OFF-time. This study supports the development of CVN424 for the treatment of PD.FundingCerevance.

2022-04-01·Journal of Pharmacology and Experimental Therapeutics

A Phase I, First-in-Human, Healthy Volunteer Study to Investigate the Safety, Tolerability, and Pharmacokinetics of CVN424, a Novel G Protein-Coupled Receptor 6 Inverse Agonist for Parkinson’s Disease

Article

作者: Margolin, David H ; Davidson, Antonia M ; Matthews, Kim L ; Brice, Nicola L ; Carlton, Mark B L

CVN424 is a novel small molecule and first-in-class candidate therapeutic to selectively modulate GPR6, an orphan G-protein coupled receptor. Expression of GPR6 is largely confined to the subset of striatal projection neurons that give rise to the indirect (striatopallidal) pathway, important in the control of movement. CVN424 improves motor function in preclinical animal models of Parkinson's disease. Here, we report results of a phase 1, first-in-human study investigating the safety, tolerability, and pharmacokinetics of CVN424 in healthy volunteers. The study (NCT03657030) was randomized, double-blind, and placebo controlled. CVN424 was orally administered in ascending doses to successive cohorts as inpatients in a clinical research unit. Single doses ranged from 1 mg to 225 mg, and repeated (7 day) daily doses were 25, 75, or 150 mg. CVN424 peak plasma concentrations were reached within 2 h post-dose in the fasted state and increased with increasing dose. Dosing after a standardized high-fat meal reduced and delayed the peak plasma concentration, but total plasma exposure was similar. Mean terminal half-life ranged from 30 to 41 h. CVN424 was generally well tolerated: no serious or severe adverse effects were observed, and there were no clinically significant changes in vital signs or laboratory parameters. We conclude that CVN424, a nondopaminergic compound that modulates a novel therapeutic target, was safe and well tolerated. A phase 2 study in patients with Parkinson's disease is underway. SIGNIFICANCE STATEMENT: This is the first-in-human clinical study of a first-in-class candidate therapeutic. CVN424 modulates a novel drug target, GPR6, which is selectively expressed in a pathway in the brain that has been implicated in the motor dysfunction of patients with Parkinson's disease. This study paves the way for investigating this novel mechanism of action in patients with Parkinson's disease.

2021-07-22·Journal of Medicinal Chemistry1区 · 医学

First-Time Disclosure of CVN424, a Potent and Selective GPR6 Inverse Agonist for the Treatment of Parkinson’s Disease: Discovery, Pharmacological Validation, and Identification of a Clinical Candidate

1区 · 医学

Article

作者: Macklin, Todd K. ; Moore, Steve ; Brown, Jason ; Sun, Huikai ; Carlton, Mark Beresford Lewis ; English, Nicole Marion ; Adams, Mark ; Kikuchi, Shota ; Green, Jason ; Collia, Deanna R. ; Schiffer, Hans H. ; Murphy, Sean T. ; Hitchcock, Stephen ; Ray, William J. ; Hopkins, Maria ; Monenschein, Holger ; Reichard, Holly A. ; Kaushal, Nidhi ; Brice, Nicola L.

Parkinson's disease (PD) is a chronic and progressive movement disorder with the urgent unmet need for efficient symptomatic therapies with fewer side effects. GPR6 is an orphan G-protein coupled receptor (GPCR) with highly restricted expression in dopamine receptor D2-type medium spiny neurons (MSNs) of the indirect pathway, a striatal brain circuit which shows aberrant hyperactivity in PD patients. Potent and selective GPR6 inverse agonists (IAG) were developed starting from a low-potency screening hit (EC₅₀ = 43 μM). Herein, we describe the multiple parameter optimization that led to the discovery of multiple nanomolar potent and selective GPR6 IAG, including our clinical compound CVN424. GPR6 IAG reversed haloperidol-induced catalepsy in rats and restored mobility in the bilateral 6-OHDA-lesioned rat PD model demonstrating that inhibition of GPR6 activity in vivo normalizes activity in basal ganglia circuitry and motor behavior. CVN424 is currently in clinical development to treat motor symptoms in Parkinson's disease.

项与 CVN-424 相关的新闻（医药）

2024-11-18

·GlobeNewswire-Health Care

Cerevance Doses First Patient in Pivotal Phase 3 ARISE Trial of Solengepras for Treatment of Parkinson’s Disease

Solengepras is a potentially first-in-class, oral, non-dopaminergic investigational therapy in development for Parkinson’s diseaseARISE will evaluate the efficacy of solengepras as an adjunctive therapy to levodopa and other background Parkinson’s disease medicationsCompany expects to report topline data in the first half of 2026 BOSTON, Nov. 18, 2024 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing multiple cell type-specific therapies for the treatment of neurodegenerative, psychiatric, and central nervous system-controlled metabolic disorders, has dosed the first patient in ARISE, a Phase 3 clinical trial evaluating the efficacy of solengepras as a potential adjunctive treatment for individuals with Parkinson’s disease. “Parkinson’s disease is the fastest growing neurological disorder globally, highlighting a significant need for more improved and effective therapies,” shared Craig Thompson, chief executive officer of Cerevance. “Unlike traditional Parkinson’s treatments that aim to restore dopamine levels, solengepras is designed to selectively target and modulate the specific brain circuits responsible for controlling movement and non-motor functions, without relying directly on dopamine pathways. This novel mechanism of action is designed to reduce motor complications such as dyskinesia and “OFF” periods, which we believe may offer potentially improved tolerability and potential impact on non-motor symptoms for individuals with Parkinson’s disease.” ARISE is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial, with a plan to enroll approximately 330 patients with three or more hours of “OFF” time per day. The primary endpoint is the change from baseline in the total daily “OFF” time at Week 12. Secondary endpoints include the change in “ON” time without troublesome dyskinesia, evaluations of motor function and quality of life, as assessed by the Movement Disorder Society-Unified Parkinson’s disease Rating Scale (MDS-UPDRS), the Epworth Sleepiness Scale (ESS), and the use of digital technologies, such as the Cogstate PD Battery (for the evaluation of cognition) and the Modality System (for the evaluation of motor/non-motor impairment). The trial will also evaluate the safety and tolerability of solengepras. “The initiation of ARISE builds on the encouraging Phase 2 data we have generated and represents an exciting chapter in Cerevance’s journey to address the unmet needs of individuals with Parkinson’s disease,” added Sagar Vaidya, M.D., Ph.D., chief medical officer of Cerevance. “We look forward to advancing solengepras through this pivotal trial and moving closer to potentially bringing a new, non-dopaminergic therapy to the Parkinson’s community.” For more information on the trial, please visit https://arise.clinicalenrollment.com or clinicaltrials.gov (NCT06553027). About Solengepras (CVN424)Solengepras is designed to provide a potentially novel approach to the treatment of Parkinson’s disease. Unlike dopaminergic therapies, which primarily act by replenishing, enhancing, or mimicking dopamine, solengepras is designed to selectively address the indirect pathway by modulating the GPR6 receptor. By inhibiting GPR6, solengepras aims to restore both motor and non-motor function without directly affecting dopamine levels or signaling, improving the relative balance between the direct and indirect pathways, and potentially reducing the risk of common side effects associated with dopaminergic therapies, such as dyskinesias and motor fluctuations. Solengepras is currently being evaluated as a once-daily, oral treatment for use as both a monotherapy (Phase 2 ASCEND clinical trial) and as an adjunctive therapy to levodopa and other anti-Parkinsonian medication (Phase 3 ARISE clinical trial). About Parkinson’s DiseaseParkinson’s disease is a progressive neurodegenerative disorder that is characterized by both motor symptoms, such as tremor, rigidity, and bradykinesia/akinesia, and non-motor symptoms, such as mood changes, apathy, and cognitive deficits. Globally, Parkinson’s disease is the fastest growing neurological disorders, affecting more than ten million people worldwide and approximately one million people in the United States. The current standard of care has primarily relied on dopaminergic therapies, which lose effectiveness over time and are associated with side effects that result in challenging risk-benefit profiles. About CerevanceCerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative, psychiatric and central nervous system (“CNS”)-controlled metabolic disorders. Our proprietary platform, Nuclear Enriched Transcript Sort sequencing (NETSseq), allows us to identify targets that are expressed at very low levels, that are present in rare cell types, or that change over time as a disease progresses. Our most advanced product candidate, solengepras (CVN424), is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both the motor and non-motor symptoms of Parkinson's disease. Our second product candidate, CVN766, is designed to be a highly selective oral antagonist of the orexin 1 receptor that we plan to evaluate in a Phase 2 study for the potential treatment of binge eating disorder and schizophrenia. Our third product candidate, CVN293, is a highly selective investigational oral inhibitor targeting potassium two pore domain channel subfamily K member 13 (KCNK13) and represents a potentially novel intervention point for neurodegenerative disorders by reducing neuroinflammation. We plan to evaluate CVN293 in a Phase 2 study for the potential treatment of frontotemporal dementia. Contacts Cerevance: Johnna Simões, ir@cerevance.com Media: Andrew Mielach, amielach@lifescicomms.com, +1-646-876-5868

临床2期临床3期

2024-11-13

·GlobeNewswire-Health Care

Cerevance’s CVN293 Demonstrated Positive Phase 1 Results in Healthy Volunteers

CVN293 was generally well-tolerated in healthy volunteers for up to 14-days of continuous dosing Dose-dependent exposure was observed with evidence of robust brain penetration Data supports potential advancement into Phase 2 for neurodegenerative diseases characterized by neuroinflammation such as Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease Nov. 11, 2024 -- Cerevance, a clinical-stage biopharmaceutical company advancing multiple cell type-specific therapies for the treatment of neurodegenerative, psychiatric, and central nervous system-controlled metabolic disorders, has reported positive results from its Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical study of CVN293 in healthy volunteers. CVN293 is designed to inhibit KCNK13, a potentially novel target involved in activating the NLRP3 inflammasome, with the aim of reducing neuroinflammation and attenuating disease progression in a variety of neurodegenerative disorders. KCNK13 was identified by Cerevance’s proprietary NETSseq platform. “We are very encouraged by the clinical data for CVN293, observing that it was generally well-tolerated and achieved favorable brain penetration,” said Mark Carlton, Ph.D., chief scientific officer and co-founder of Cerevance. “CVN293 selectively inhibits KCNK13, a gene selectively expressed in microglia with minimal expression in peripheral tissues. This selective targeting may contribute to its favorable tolerability profile. By inhibiting KCNK13 to reduce NLRP3 activation, CVN293 may offer a disease-modifying approach for challenging CNS disorders.” CVN293 was generally well-tolerated in healthy participants with single doses up to 1000mg and multiple doses of up to 375mg twice daily for 14 days. No serious adverse events were reported and all participants completed the study. All related treatment-emergent adverse events were mild. Dose-dependent increases in CVN293 exposure were observed, achieving plasma concentrations that align with clinically relevant levels as indicated by preclinical studies. CSF sampling demonstrated high brain penetrance of CVN293. Clinical safety and pharmacokinetic profile of CVN293 is favorable for potential advancement into Phase 2 studies. The Phase 1 study of CVN293 was a first-in-human, randomized, placebo-controlled, single-center, SAD and MAD study in 72 healthy adult volunteers. The primary objective of the study was to evaluate the safety, tolerability, and pharmacokinetics of oral CVN293. In the SAD portion of the study, a single dose of CVN293 ranging from 3 mg to 1000 mg or placebo were administered to 48 healthy adult participants (CVN293 n=36; placebo n=12). In the MAD portion of the study, CVN293 doses from 50 mg (25 mg twice daily) to 750 mg (375 mg twice daily) or placebo were administered to 24 healthy adult participants (CVN293 n=18; placebo n=6) over 14 consecutive days. CVN293 is a highly-selective oral inhibitor targeting KCNK13, a potassium two pore domain channel subfamily K member 13, which is implicated in neuroinflammation and central nervous system disorders. By targeting KCNK13, identified to be solely expressed in microglia with Cerevance’s proprietary NETSseq platform, CVN293 aims to reduce the activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome specifically in the brain. This inflammasome plays a critical role in the activation of microglia, which are associated with neurodegenerative disorders such as Alzheimer’s disease and frontotemporal dementia. In contrast to other therapies that target NLRP3 which may suppress aspects of the peripheral immune system, we believe the selective inhibition of KCNK13 by CVN293 in microglia may provide better tolerability relative to other approaches targeting NLRP3 and has the potential to act as a disease-modifying treatment by specifically targeting neuroinflammation in the brain. Cerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative, psychiatric and central nervous system (“CNS”)-controlled metabolic disorders. Our proprietary platform, Nuclear Enriched Transcript Sort sequencing (NETSseq), allows us to identify novel targets, even those that are expressed at very low levels, that are present in rare cell types, or that change over time as a disease progresses. Our most advanced product candidate, solengepras (CVN424), is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both the motor and non-motor symptoms of Parkinson's disease. Our second product candidate, CVN766, is designed to be a highly selective oral antagonist of the orexin 1 receptor that we plan to evaluate in a Phase 2 study for the potential treatment of binge eating disorder and schizophrenia. Our third product candidate, CVN293, is a highly selective investigational oral inhibitor targeting potassium two pore domain channel subfamily K member 13 (KCNK13) and represents a potentially novel intervention point for neurodegenerative disorders by reducing neuroinflammation. We plan to evaluate CVN293 in a Phase 2 study for the potential treatment of frontotemporal dementia. The content above comes from the network. if any infringement, please contact us to modify.

临床结果

2024-10-21

·BioSpace

Cerevance Announces Publication of Positive Phase 2 Results of Solengepras for the Treatment of Parkinson’s Disease in eClinicalMedicine

BOSTON, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Cerevance, a clinical-stage biopharmaceutical company advancing multiple cell type-specific therapies for the treatment of neurodegenerative, psychiatric, and central nervous system-controlled metabolic disorders, has published the full results from the Phase 2 clinical trial of solengepras, in eClinicalMedicine , a peer-reviewed journal published by The Lancet Discovery Science Suite . The results demonstrated that solengepras, a potentially first-in-class, oral, once-daily, non-dopaminergic, GPR6 inverse agonist, significantly reduced OFF time in individuals with Parkinson’s disease and was generally well-tolerated. The Phase 2 clinical trial met the key efficacy endpoint and demonstrated a reduction in average daily OFF time from baseline at Day 27, as recorded over two days using a self-reported patient motor diary. On Day 27, the change from baseline in daily OFF time was -1.6 hours (p 5%) were headache and nausea which were generally mild and transient. “We are excited to share the results of this important Phase 2 study with the broader scientific community through this publication in eClinicalMedicine,” said chief executive officer, Craig Thompson. “The data demonstrated solengepras’ potential to be a meaningful therapeutic option for individuals with Parkinson’s disease, addressing not only motor symptoms but also overall quality-of-life.” For more information on the Phase 2 clinical trial and to access the full publication, visit About Solengepras (CVN424) Solengepras is designed to provide a potentially novel approach to the treatment of Parkinson’s disease. Unlike dopaminergic therapies, which primarily act by replenishing, enhancing, or mimicking dopamine, solengepras is designed to selectively address the indirect pathway by modulating the GPR6 receptor. By inhibiting GPR6, solengepras aims to restore both motor and non-motor function without directly affecting dopamine levels or signaling, improving the relative balance between the direct and indirect pathways, and potentially reducing the risk of common side effects associated with dopaminergic therapies, such as dyskinesias and motor fluctuations. Solengepras is currently being evaluated as a once-daily, oral treatment for use as both a monotherapy (Phase 2 ASCEND clinical trial) and as an adjunctive therapy to levodopa and other anti-Parkinsonian medication (Phase 3 ARISE clinical trial). About Parkinson’s Disease Parkinson’s disease is a progressive neurodegenerative disorder that is characterized by both motor symptoms, such as tremor, rigidity, and bradykinesia/akinesia, and non-motor symptoms, such as mood changes, apathy, and cognitive deficits. Globally, Parkinson’s disease is the fastest growing neurological disorders, affecting more than ten million people worldwide and approximately one million people in the United States. The current standard of care has primarily relied on dopaminergic therapies, which lose effectiveness over time and are associated with side effects that result in challenging risk-benefit pro About Cerevance Cerevance is focused on advancing cell type-specific therapies for the treatment of neurodegenerative, psychiatric and central nervous system (“CNS”)-controlled metabolic disorders. Our proprietary platform, N uclear E nriched T ranscript S ort seq uencing (NETSseq), allows us to identify targets that are expressed at very low levels, that are present in rare cell types, or that change over time as a disease progresses. Our most advanced product candidate, solengepras (CVN424), is currently in Phase 3 development and has the potential to be a first-in-class, oral non-dopaminergic therapy for both the motor and non-motor symptoms of Parkinson’s disease. Our second product candidate, CVN766, is designed to be a highly selective oral antagonist of the orexin 1 receptor that we plan to evaluate in a Phase 2 study for the potential treatment of binge eating disorder and schizophrenia. Our third product candidate, CVN293, is a highly selective investigational oral inhibitor targeting potassium two pore domain channel subfamily K member 13 (KCNK13) and represents a potentially novel intervention point for neurodegenerative disorders by reducing neuroinflammation. We plan to evaluate CVN293 in a Phase 2 study for the potential treatment of frontotemporal dementia. Contacts Cerevance: Johnna Simões, ir@cerevance.com Media: Andrew Mielach, amielach@lifescicomms.com, +1-646-876-5868

临床2期临床结果临床3期

100 项与 CVN-424 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
并发症	临床3期	美国	Cerevance, Inc.初创企业	2024-09-20
帕金森病	临床3期	美国	Cerevance, Inc.初创企业	2024-09-20

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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


NCT04191577 (Biospace) 人工标引	临床2期	帕金森病	-	solengepras 50 mg	(鏇淵遞網製齋鹹鏇遞觸) = 鹽顧願簾襯齋鏇襯鹹餘齋網糧獵窪範糧鏇糧壓 (糧餘艱觸築鏇鏇鏇網淵 )	积极	2024-10-21
				solengepras 150 mg	(鏇淵遞網製齋鹹鏇遞觸) = 繭簾夢選鑰顧齋醖積餘齋網糧獵窪範糧鏇糧壓 (糧餘艱觸築鏇鏇鏇網淵 )
NCT05635461 (CTgov)	临床1期	帕金森病	32	CVN424 (Treatment A: CVN424 150 mg Suspension (Fasted))	觸鏇觸淵糧膚鬱鹹糧蓋(鏇鏇積醖願壓襯襯醖夢) = 蓋鹽簾餘憲廠積鑰餘繭糧壓憲構鹽鬱獵網鏇壓 (鑰範構餘壓醖齋醖製壓, 餘鬱築鏇壓蓋衊遞襯顧 ~ 淵簾蓋網遞鹹鹽鏇製襯) 更多	-	2024-08-15
				CVN424 (Treatment B: CVN424 150 mg Tablet (Fasted))	觸鏇觸淵糧膚鬱鹹糧蓋(鏇鏇積醖願壓襯襯醖夢) = 鬱構選遞積窪醖艱顧範糧壓憲構鹽鬱獵網鏇壓 (鑰範構餘壓醖齋醖製壓, 膚築製築夢鬱夢製廠顧 ~ 衊構選齋簾窪簾衊製網) 更多
NCT04191577 (CTgov)	临床2期	精神运动障碍 \| 帕金森病	136	Placebo (Placebo Arm)	艱衊夢齋廠鬱廠築願積(夢願艱蓋餘網廠獵齋願) = 獵衊網餘蓋積蓋蓋願衊繭鑰壓鑰選網築鬱艱糧 (鹽鹹糧繭繭顧製鹹廠壓, 廠簾選網鏇壓網簾蓋糧 ~ 簾觸醖構網鏇醖積選廠) 更多	-	2024-07-03
				CVN424 (CVN424 50 mg)	艱衊夢齋廠鬱廠築願積(夢願艱蓋餘網廠獵齋願) = 鹽夢夢憲網鹹糧遞糧憲繭鑰壓鑰選網築鬱艱糧 (鹽鹹糧繭繭顧製鹹廠壓, 繭夢艱鹽鬱憲鬱鬱鑰構 ~ 鏇築獵製淵衊製鏇繭鬱) 更多