A Randomized, Double-Blind Phase1b/2a Clinical Study to Evaluate Efficacy, Safety and Tolerability of Subcutaneous Administration of NP-201 Acetate Injection in Healthy Adult Volunteers and in Patients With Mild-To-Moderate Active Ulcerative Colitis

This Phase 1b/2a clinical development plan is focused on the use of NP-201 acetate injection to investigate the pharmacokinetics (PK), safety, efficacy, PD (pharmacodynamic) markers (Phase 1b) and tolerability of NP-201 acetate injection after subcutaneous (SC) injection of multiple doses in healthy adults and in the ulcerative colitis (UC) patient population.

Start Date25 Nov 2024

Sponsor / Collaborator

NIBEC Co., Ltd.

CTR20234022

/ CompletedNot Applicable

盐酸罗匹尼罗片在健康受试者中空腹和餐后状态下的单剂量、随机、开放、两周期、两序列、自身交叉设计的生物等效性试验

[Translation] A single-dose, randomized, open-label, two-period, two-sequence, self-crossover bioequivalence study of ropinirole hydrochloride tablets in healthy subjects under fasting and fed conditions

主要研究目的：研究空腹和餐后状态下单次口服受试制剂盐酸罗匹尼罗片（规格：0.25mg，持证商：宏越科技（湖州）有限公司）与参比制剂盐酸罗匹尼罗片（商品名：Requip®，规格：0.25mg，持证商：グラクソ.スミスクライン株式会社）在健康成年受试者体内的药代动力学，评价两种制剂的生物等效性。次要研究目的：评价健康受试者空腹和餐后单次口服受试制剂（T）盐酸罗匹尼罗片和参比制剂（R）盐酸罗匹尼罗片（Requip®）后的安全性。

[Translation]

Main study objectives: To study the pharmacokinetics of the test preparation ropinirole hydrochloride tablets (specification: 0.25 mg, licensee: Hongyue Technology (Huzhou) Co., Ltd.) and the reference preparation ropinirole hydrochloride tablets (trade name: Requip®, specification: 0.25 mg, licensee: Graphos. Smiscline Co., Ltd.) in healthy adult subjects after a single oral administration in the fasting and fed state, and to evaluate the bioequivalence of the two preparations. Secondary study objectives: To evaluate the safety of the test preparation (T) ropinirole hydrochloride tablets and the reference preparation (R) ropinirole hydrochloride tablets (Requip®) after a single oral administration in healthy subjects after fasting and feeding.

Start Date09 Jan 2024

Sponsor / Collaborator

Hongyue Technology (Huzhou) Co., Ltd.

CTR20233125

/ CompletedNot Applicable

盐酸罗匹尼罗缓释片在中国健康受试者中单中心、随机、开放、单次给药、两制剂、两周期交叉人体生物等效性试验

[Translation] A single-center, randomized, open-label, single-dose, two-formulation, two-period crossover bioequivalence study of ropinirole hydrochloride extended-release tablets in Chinese healthy subjects

主要研究目的：以植恩生物技术股份有限公司生产的盐酸罗匹尼罗缓释片（规格：2mg）为受试制剂（T），按有关生物等效性试验的规定，以持证商为GLAXO SMITHKLINE,S.A.的盐酸罗匹尼罗缓释片（规格：2mg，商品名：力备®）为参比制剂（R）进行生物等效性试验。次要研究目的：观察受试制剂和参比制剂盐酸罗匹尼罗缓释片在健康受试者中的安全性。

[Translation]

The main purpose of the study: Ropinirole hydrochloride sustained-release tablets (specification: 2 mg) produced by Zhien Biotechnology Co., Ltd. were used as the test preparation (T), and Ropinirole hydrochloride sustained-release tablets (specification: 2 mg, trade name: Libei®) produced by GLAXO SMITHKLINE, S.A. were used as the reference preparation (R) for bioequivalence test according to the relevant provisions of bioequivalence test. Secondary purpose of the study: To observe the safety of the test preparation and the reference preparation Ropinirole hydrochloride sustained-release tablets in healthy subjects.

Start Date13 Oct 2023

Sponsor / Collaborator

Chongqing Zhi'en Pharmaceutical Co., Ltd.

100 Clinical Results associated with Ropinirole Hydrochloride

100 Translational Medicine associated with Ropinirole Hydrochloride

100 Patents (Medical) associated with Ropinirole Hydrochloride

Literatures (Medical) associated with Ropinirole Hydrochloride

01 Feb 2025·JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

Spinal cord motor neuron phenotypes and polygenic risk scores in sporadic amyotrophic lateral sclerosis: deciphering the disease pathology and therapeutic potential of ropinirole hydrochloride

Letter

Author: Morimoto, Satoru ; Okano, Hideyuki ; Wang, Qingbo S ; Okada, Yukinori ; Kato, Chris ; Takahashi, Shinichi ; Namba, Shinichi

07 Aug 2024·ACS Applied Materials & Interfaces

3D Printed Drug Delivery Systems in Action–Magnetic Resonance Imaging and Relaxometry for Monitoring Mass Transport Phenomena

Article

Author: Dorożyński, Przemysław ; Milanowski, Bartłomiej ; Birczyński, Artur ; Baran, Ewelina ; Kulinowski, Piotr ; Klaja, Jolanta ; Nowak, Piotr

The hypothesis of the study was that (1) 3D printed drug delivery systems (DDS) could be characterized in situ during drug release using NMR/MRI techniques in terms of mass transport phenomena description (interfacial phenomena), particularly for systems dealing with two mobile phases (e.g., water and low molecular weight liquid polymer); (2) consequently, it could be possible to deduce how these interfacial mass transport phenomena influence functional properties of 3D printed DDS. Matrix drug delivery systems, prepared using masked stereolithography (MSLA), containing poly(ethylene glycol) diacrylate (PEGDA) and low molecular weight polyethylene glycol (PEG) with ropinirole hydrochloride (RH) were studied as example formulations. The PEGDA to PEG (mobile phase) concentration ratio influenced drug release. It was reflected in spatiotemporal changes in parametric T₂ relaxation time (T₂) and amplitude (A) images obtained using magnetic resonance imaging (MRI) and T₁-T₂ relaxation time correlations obtained using low-field time-domain nuclear magnetic resonance (LF TD NMR) relaxometry during incubation in water. For most of the tested formulations, two signal components related to PEG and water were assessed in the hydrated matrices by MRI relaxometry (parametric T₂/A images). The PEG component faded out due to outward PEG diffusion and was gradually replaced by the water component. Both components spatially and temporally changed their parameters, reflecting evolving water-polymer interactions. The study shows that dynamic phenomena related to bidirectional mass transport can be quantified in situ using NMR and MRI techniques to gain insight into drug release mechanisms from 3D printed DDS systems.

01 Dec 2023·Journal of neurochemistry

Induced pluripotent stem cells‐based disease modeling, drug screening, clinical trials, and reverse translational research for amyotrophic lateral sclerosis

Review

Author: Morimoto, Satoru ; Kato, Chris ; Nakahara, Jin ; Takahashi, Shinichi ; Okano, Hideyuki

Abstract:

It has been more than 10 years since the hopes for disease modeling and drug discovery using induced pluripotent stem cell (iPSC) technology boomed. Recently, clinical trials have been conducted with drugs identified using this technology, and some promising results have been reported. For amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, several groups have identified candidate drugs, ezogabine (retigabine), bosutinib, and ropinirole, using iPSCs‐based drug discovery, and clinical trials using these drugs have been conducted, yielding interesting results. In our previous study, an iPSCs‐based drug repurposing approach was utilized to show the potential of ropinirole hydrochloride (ROPI) in reducing ALS‐specific pathological phenotypes. Recently, a phase 1/2a trial was conducted to investigate the effects of ropinirole on ALS further. This double‐blind, randomized, placebo‐controlled study confirmed the safety and tolerability of and provided evidence of its ability to delay disease progression and prolong the time to respiratory failure in ALS patients. Furthermore, in the reverse translational research, in vitro characterization of patient‐derived iPSCs‐motor neurons (MNs) mimicked the therapeutic effects of ROPI in vivo, suggesting the potential application of this technology to the precision medicine of ALS. Interestingly, RNA‐seq data showed that ROPI treatment suppressed the sterol regulatory element‐binding protein 2‐dependent cholesterol biosynthesis pathway. Therefore, this pathway may be involved in the therapeutic effect of ROPI on ALS. The possibility that this pathway may be involved in the therapeutic effect of ALS was demonstrated. Finally, new future strategies for ALS using iPSCs technology will be discussed in this paper.

News (Medical) associated with Ropinirole Hydrochloride

02 Jun 2023

·www.sciencedaily.com

Parkinson's disease drug ropinirole safely slowed the progression of ALS for over 6 months in a clinical trial

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal motor neuron disease that causes people to gradually lose control of their muscles. There is no cure, and current treatments focus on reducing symptoms and providing supportive care. Researchers now show in an early clinical trial that the Parkinson's disease drug ropinirole is safe to use in ALS patients and delayed disease progression by 27.9 weeks on average. Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal motor neuron disease that causes people to gradually lose control of their muscles. There is no cure, and current treatments focus on reducing symptoms and providing supportive care. Reporting June 1 in the journal Cell Stem Cell, researchers from Japan show in an early clinical trial that the Parkinson's disease drug ropinirole is safe to use in ALS patients and delayed disease progression by 27.9 weeks on average. Some patients were more responsive to ropinirole treatment than others, and the researchers were able to predict clinical responsiveness in vitro using motor neurons derived from patient stem cells. "ALS is totally incurable, and it's a very difficult disease to treat," says senior author and physiologist Hideyuki Okano of the Keio University School of Medicine in Tokyo. "We previously identified ropinirole as a potential anti-ALS drug in vitro by iPSC drug discovery, and with this trial, we have shown that it is safe to use in ALS patients and that it potentially has some therapeutic effect, but to confirm its effectiveness we need more studies, and we are now planning a phase 3 trial for the near future." To test ropinirole's safety and effectiveness in patients with sporadic (i.e., non-familial) ALS, the team recruited 20 patients receiving care at Keio University Hospital in Japan. None of the patients carried genes predisposing to the disease, and, on average, they had been living with ALS for 20 months. The trial was double blinded for the first 24 weeks, meaning that the patients and doctors did not know which patients were receiving ropinirole and which were receiving a placebo. Then, for the following 24 weeks, all patients who wished to continue were knowingly administered ropinirole. Many patients dropped out along the way -- partially due to the COVID-19 pandemic -- so only 7/13 ropinirole-treated and 1/7 placebo-followed-by-ropinirole-treated patients were monitored for the full year. However, no patients dropped out due to safety reasons. To determine whether the drug was effective at slowing the progression of ALS, the team monitored a variety of different measures throughout the trial and for 4 weeks after treatment concluded. These included changes in the patients' self-reported physical activity and ability to eat and drink independently, activity data from wearable devices, and physician-measured changes in mobility, muscle strength, and lung function. "We found that ropinirole is safe and tolerable for ALS patients and shows therapeutic promise at helping them sustain daily activity and muscle strength," says first author Satoru Morimoto, a neurologist at the Keio University School of Medicine in Tokyo. Patients who received ropinirole during both phases of the trial were more physically active than patients in the placebo group. They also showed slower rates of decline in mobility, muscle strength, and lung function, and they were more likely to survive. The benefits of ropinirole relative to the placebo became increasingly pronounced as the trial progressed. However, placebo group patients who began taking ropinirole halfway through the trial did not experience these improvements, which suggests that ropinirole treatment may only be useful if treatment is started earlier and administered over a longer duration. Next, the researchers investigated the mechanisms behind ropinirole's effects and looked for molecular markers of the disease. To do this, they generated induced pluripotent stem cells from the patients' blood and grew these cells into motor neurons in the lab. Compared to healthy motor neurons, they found that motor neurons from ALS patients showed distinct differences in structure, gene expression, and metabolite concentrations, but ropinirole treatment reduced these differences. Specifically, motor neurons grown from ALS patients had shorter neurites compared to healthy motor neurons, but these axons grew to a more normal length when the cells were treated with ropinirole. The team also identified 29 genes related to cholesterol synthesis that tended to be upregulated in motor neurons from ALS patients, but ropinirole treatment suppressed their gene expressions over time. They also identified lipid peroxide as a good surrogate marker for estimating the effect of ropinirole both in vitro and clinically. "We found a very striking correlation between a patient's clinical response and the response of their motor neurons in vitro," says Morimoto. "Patients whose motor neurons responded robustly to ropinirole in vitro had a much slower clinical disease progression with ropinirole treatment, while suboptimal responders showed much more rapid disease progression despite taking ropinirole." The researchers say that this suggests that this method -- of growing and testing motor neurons from patient-derived induced pluripotent stem cells -- could be used clinically to predict how effective the drug would be for a given patient. It's unclear why some patients are more responsive to ropinirole than others, but the researchers think that it's probably due to genetic differences that they hope to pinpoint in future studies.

Clinical ResultPhase 3Drug ApprovalPhase 2

25 Oct 2022

·www.prnewswire.com

HOLOGENIX, CREATORS OF CELLIANT®, AND UNIFI®, MAKERS OF REPREVE®, ANNOUNCE PARTNERSHIP

Hologenix, LLC, Inventors of Celliant (PRNewsfoto/Hologenix, LLC) REPREVE® logo » Two Innovators Team Up to Introduce CELLIANT® with REPREVE®, a Performance Fiber from Recycled Materials with Infrared Wellness Benefits » LOS ANGELES, Oct. 25, 2022 /PRNewswire/ -- Materials science leader Hologenix, creators of CELLIANT®, and global textile solutions provider UNIFI®, makers of REPREVE®, have announced their partnership to introduce CELLIANT® with REPREVE®. CELLIANT with REPREVE has the infrared properties of science-backed CELLIANT infrared technology and the sustainable footprint of REPREVE, the world's number one brand of recycled fiber. CELLIANT is a blend of IR-generating bioceramic minerals, which, when embedded into textiles, allows them to convert body heat into infrared energy, returning it to the body and temporarily increasing local circulation and cellular oxygenation. This aids significantly in muscle recovery, increases endurance, and improves overall performance in healthy individuals, among other benefits. REPREVE recycled performance fiber consists of high-quality fibers made from 100% recycled materials, including post-consumer plastic bottles and pre-consumer waste. It is also certified and traceable with U TRUST® verification and FiberPrint™ technology, to back up customers' recycled claims. Compared to virgin fiber, REPREVE helps to offset the use of petroleum, emitting fewer greenhouse gasses and conserving water and energy in the process. Both CELLIANT and REPREVE are key ingredients in world-class brands across many sectors, from apparel and sportswear to upholstery fabric and more, so the partnership opens an array of possible applications. No doubt for brands that are already utilizing both CELLIANT and REPREVE independently, the CELLIANT with REPREVE union is a welcome innovation. CELLIANT with REPREVE's official preferred North America knitting partner is Beverly Knits, one of the largest circular knitters in the US, developing fabric for all markets including intimate apparel, activewear, outdoor products, mattress and bedding, automotive, industrial and medical. Beverly Knits also operates Creative Dyeing & Finishing, LLC. The three-way partnership allows for the production of finished goods to take place within a 300-mile radius, from CELLIANT mineral processing to final product. "We are honored to partner with sustainability leader Unifi and its REPREVE fiber," said Seth Casden, Hologenix Co-Founder and CEO. "CELLIANT with REPREVE marries self-care and sustainability for a new generation of products." Eddie Ingle, Chief Executive Officer of UNIFI, continued, "We're excited that the infrared component of CELLIANT with REPREVE provides enhanced health and wellness benefits and that we are expanding the use of sustainable fiber options that positively impact our planet, both now and in the future." "It is a core part of our ethos to provide Made in USA products that support American manufacturing," added Ron Sytz, Chief Executive Officer of Beverly Knits. "To further this aim while simultaneously creating products that are both better for the consumer and better for the earth is something we can all be proud of." About Hologenix and CELLIANT Hologenix, LLC, headquartered in Pacific Palisades, California, is a materials science company innovating products that energize all aspects of life. Its flagship innovation, CELLIANT®, is a science-backed infrared (IR) technology that improves health and wellness by promoting restful sleep and enhancing performance and recovery. CELLIANT's natural blend of IR-generating minerals is embedded into fibers, yarns and fabrics, powering bio-responsive textiles. CELLIANT is a key ingredient used by world-class brands in products spanning apparel, sleepwear, bedding, upholstery, uniforms and medical supplies. CELLIANT is rigorously tested by a Science Advisory Board composed of experts in photobiology, nanotechnology, sleep medicine, and diabetes and wound care. The Science Advisory Board has overseen nine peer-reviewed published studies that demonstrate CELLIANT's effectiveness and the benefits of infrared energy. For more information, visit celliant.com. About Unifi, Inc. Unifi, Inc. (NYSE: UFI) is a global textile solutions provider and one of the world's leading innovators in manufacturing synthetic and recycled performance fibers. Through REPREVE®, the global leader in recycled performance fibers, Unifi has transformed more than 34 billion plastic bottles into recycled fiber for new apparel, footwear, home goods, and other consumer products. As an industry leader, Unifi owns and operates vertically integrated, large-scale manufacturing facilities across the U.S. and major textile regions globally, and operates with a foundational commitment to ethical and sustainable practices that are consistent throughout its supply chain. Unifi's ESG-compliant model is ingrained in the company's long-term business strategy. For more information on Unifi and its dedication to its ESG focused innovation and initiatives, visit . About REPREVE® Made by Unifi, Inc. (NYSE: UFI), REPREVE® is the global leader in recycled performance fibers. Leveraging its proprietary regeneration technology, REPREVE® has transformed more than 34 billion plastic bottles into recycled fiber that is trusted by leading brands to power sustainable consumer goods worldwide. REPREVE® offers advanced fiber technology that delivers enhanced comfort, greater performance, superior durability, thermal regulation, and more. As the only eco-performance fiber with U TRUST® verification to certify transparency and traceability, REPREVE® empowers brands and consumers to champion sustainability. As a catalyst for change, REPREVE® is committed to leading the global shift towards a more sustainable future by innovating today. For more information about REPREVE ®, visit . REPREVE® is a trademark of Unifi, Inc. About Beverly Knits Beverly Knits is one of the largest circular knitters in the United States. The company has created industry-leading solutions for some of the world's greatest brands of athletic wear, intimate apparel, bedding, automotive fabrics, and industrial fabrics. The ability to innovate and respond quickly to changing demands has been a hallmark of Beverly Knits since its founding in 1980. Beverly Knits currently operates over 300 circular knitting machines, which produce over 30 million square yards of fabric annually. The company's manufacturing and warehousing facilities cover over 450,000 square feet in five buildings located in Gastonia, North Carolina, 55,000 square feet in Albemarle, NC, and 50,000 square feet in Hemingway, SC. To learn more, visit beverlyknits.com. For high-res images: SOURCE Hologenix,LLC/Unifi, Inc.

100 Deals associated with Ropinirole Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00784	Ropinirole Hydrochloride	N04BC04	DBSALT000390

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Parkinson Disease	GB	GSK Plc	08 Jul 1996
Restless Legs Syndrome	GB	GSK Plc	08 Jul 1996

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder	Phase 3	DE	GSK Plc	01 Jun 2006
Dyskinesias	Phase 3	US	GSK Plc	01 Dec 2003
Amyotrophic Lateral Sclerosis	Phase 2	JP	Keio University School of Medicine	01 Jun 2023
Primary Parkinson's disease	Phase 2	CN	Zhejiang Huahai Pharmaceutical Co., Ltd.	12 Apr 2013
Fibromyalgia	Phase 2	BE	GSK Plc	01 Nov 2004
Fibromyalgia	Phase 2	DK	GSK Plc	01 Nov 2004
Fibromyalgia	Phase 2	FI	GSK Plc	01 Nov 2004
Fibromyalgia	Phase 2	FR	GSK Plc	01 Nov 2004
Fibromyalgia	Phase 2	DE	GSK Plc	01 Nov 2004
Fibromyalgia	Phase 2	IT	GSK Plc	01 Nov 2004

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03250117 (CTgov)	Phase 1/2	Parkinson Disease	6	Ropinirole Implant	qgnduhwqhg(gzdvzpgvyx) = ifncvupqie jdqytzermy (wjcazujyhf, ynvnfflsnz - zimwhxdldj) View more	-	06 May 2023
NCT03038308 (CTgov)	Phase 1/2	Hyperprolactinemia \| Prolactinoma	16	Ropinirole	thoazzrcfb(wcsnwinrkr) = cegsvlssnt bfgqkjbtda (xfjohoidfo, oovjvtucgc - rzzhvexawv) View more	-	30 Jul 2021
MON-282 (ENDO2020)	Not Applicable	Hyperprolactinemia	10	Ropinirole	ewymmbbniq(gosbovijdp) = bfpgqxmipi xpjfdkrcts (zzvxpooans ) View more	Positive	08 May 2020
NCT00256854 (CTgov)	Phase 3	Restless Legs Syndrome	135	Ropinirole CR 2 mg Placebo+Ropinirole CR 2 mg (Ropinirole Cohort A1: 1 mg IR/2 mg CR-RLS/1 mg IR/1 mg IR)	xjssuwzeiv(ijmbjqnufy) = rawtaayenj rlxvpzbxoq (stcyabmhgl, rsjnxaxper - jdnkitpxmq) View more	-	15 Mar 2019
				Ropinirole CR 2 mg Placebo+Ropinirole CR 2 mg (Ropinirole Cohort A2: 1 mg IR/1 mg IR/1 mg IR/2 mg CR-RLS)	xjssuwzeiv(ijmbjqnufy) = ofxjvoasdz rlxvpzbxoq (stcyabmhgl, dnarvmjnjx - tcxreadxdm) View more
NCT01393457 (CTgov)	Phase 2	Cocaine-Related Disorders	119	levodopa/carbidopa+Ropinirole 2 mg/d (Ldopa + Ropinirole Low Dose)	fohgaktlmi(kytwvmmhff) = oqfffehuvg jcpxdirjnl (lqhawegubs, leounpyxte - dixjorrmef) View more	-	29 Mar 2018
				levodopa/carbidopa+Ropinirole 4 mg/d (Ldopa + Ropinirole High Dose)	fohgaktlmi(kytwvmmhff) = afwkkyvjtd jcpxdirjnl (lqhawegubs, zfscsaoxdk - mchtoyqfwm) View more
NCT01929317 (Pubmed \| Parkinsonism Relat Disord) Manual	Phase 3	Parkinson Disease	81	ropinirole (high-dose ropinirole CR group)	wloqolaijv(bjcvkrbpxl) = yzohxfshxl nabnckbsgf (vakxqdcpku, 5.95)	Positive	01 Jul 2017
				ropinirole (maintenance ropinirole CR 16 mg/day group)	wloqolaijv(bjcvkrbpxl) = qrsxubqghl nabnckbsgf (vakxqdcpku, 5.18)
NCT00632736 (Pubmed \| Int J Neurosci) Manual	Phase 3	Parkinson Disease	419	ropinirole	galtcfqvkk(bpzmfzydvx) = bzmzisddqo ipazhaddrb (qpthunxdkx ) View more	Positive	01 Jan 2016
NCT01494532 (TANDEM-569, CTgov)	Phase 4	Parkinson Disease	352	Placebo (Treatment Group A: Placebo)	thpphqkfsy(rgqgpjxaen) = lvvtgmbrpy afbupmrkfn (lkffqteqew, cvpfodpssu - gzmyrfpjsz) View more	-	03 Dec 2015
				placebo (Treatment Group B: 4 mg/Day)	thpphqkfsy(rgqgpjxaen) = ejdoatdpwg afbupmrkfn (lkffqteqew, mcrathpkvr - gtjopcapqa) View more
NCT01929317 (CTgov)	Phase 3	Parkinson Disease	81	Ropinirole CR+Ropinirole (Ropinirole CR - High Dose Group)	cgcgoheguw(togkhqpcfk) = mfiztfndee ivpbjenjiv (osqxsstrwu, xubrvouaua - fqhatecxqs) View more	-	21 May 2015
				Ropinirole (Ropinirole CR - Maintenance Dose Group)	qpgimqnmwv(gevirkpmzn) = cfxsgararc glkwzqtdvl (dfmbqjkjvz, emxljpzopz - tcpldivsrz) View more

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