A Randomised, Single Dose, 5-period, 5-treatment, Crossover Study to Assess the Relative Bioavailability of 4 Different Formulations of Verinurad and Allopurinol in Healthy Subjects

This study is a single centre, randomised, open-label, single-dose, 5-period, 5-treatment, crossover study in healthy male and female subjects. This study is intended to assess the relative bioavailability between the fixed dose combination (FDC, i.e. verinurad/allopurinol FDC capsule 12/300 mg) and free combination formulations of verinurad (i.e. verinurad prolonged release Hydroxypropyl methylcellulose [HPMC] capsule 12 mg) and allopurinol (i.e. allopurinol table 300 mg) in fasted and fed conditions. The study will also assess the relative bioavailability between a formulation only containing verinurad (i.e. verinurad prolonged release gelatin capsule 12 mg) and the FDC capsule.

开始日期2021-04-13

申办/合作机构

AstraZeneca PLC

[+1]

NCT04532918 / Completed临床1期

An Open-label, 3-Treatment, 3-Period, Fixed Sequence Study in Healthy Subjects to Assess the Pharmacokinetics of Verinurad and Allopurinol When Administered Alone, and in Combination With Single Doses of Cyclosporine or Rifampicin

This Phase 1 study aims to quantify the effects of cyclosporine, a broad transporter inhibitor, and rifampicin, an OATP1B1/3 inhibitor, on verinurad pharmacokinetics (PK). The study is conducted in accordance with Food and Drug Administration guidance on Clinical Drug Interaction Studies, 2020. Verinurad will be developed as a fixed combination since it will always be administered together with allopurinol.

开始日期2020-09-10

申办/合作机构

AstraZeneca PLC

[+1]

EUCTR2019-004862-16-DE / Not yet recruiting临床2期

A Phase 2, Multicentre, Double-Blind, Placebo and Active Control Efficacyand Safety Study to Evaluate Verinurad combined with Allopurinol in HeartFailure with Preserved Ejection Fraction - AMETHYST

开始日期2020-06-03

申办/合作机构

AstraZeneca AB

100 项与 Verinurad 相关的临床结果

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100 项与 Verinurad 相关的转化医学

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100 项与 Verinurad 相关的专利（医药）

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项与 Verinurad 相关的文献（医药）

2024-10-01·JAMA Cardiology

Verinurad Plus Allopurinol for Heart Failure With Preserved Ejection Fraction

Article

作者: Kitzman, Dalane W. ; Sjöström, C. David ; Mentz, Robert J. ; Voors, Adriaan A. ; Shah, Sanjiv J. ; Källgren, Christian ; Myte, Robin ; Perl, Shira ; Lewis, Gregory D. ; Kaguthi, Grace

Importance:

Elevated serum uric acid (SUA) level may contribute to endothelial dysfunction; therefore, SUA is an attractive target for heart failure with preserved ejection fraction (HFpEF). However, to the authors’ knowledge, no prior randomized clinical trials have evaluated SUA lowering in HFpEF.

Objective:

To investigate the efficacy and safety of the novel urate transporter–1 inhibitor, verinurad, in patients with HFpEF and elevated SUA level.

Design, Setting, and Participants:

This was a phase 2, double-blind, randomized clinical trial (32-week duration) conducted from May 2020 to April 2022. The study took place at 59 centers in 12 countries and included patients 40 years and older with HFpEF and SUA level greater than 6 mg/dL. Data were analyzed from August 2022 to May 2024.

Interventions:

Eligible patients were randomized 1:1:1 to once-daily, oral verinurad, 12 mg, plus allopurinol, 300 mg; allopurinol, 300 mg, monotherapy; or placebo for 24 weeks after an 8-week titration period. Allopurinol was combined with verinurad to prevent verinurad-induced urate nephropathy, and the allopurinol monotherapy group was included to account for allopurinol effects in the combination therapy group. All patients received oral colchicine, 0.5 to 0.6 mg, daily for the first 12 weeks after randomization.

Main Outcomes and Measures:

Key end points included changes from baseline to week 32 in peak oxygen uptake (VO2), Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS), and SUA level; and safety/tolerability (including adjudicated cardiovascular events).

Results:

Among 159 randomized patients (53 per treatment group; median [IQR] age, 71 [40-86] years; 103 male [65%]) with median (IQR) N-terminal pro–brain natriuretic peptide level of 527 (239-1044) pg/mL and SUA level of 7.5 (6.6-8.4) mg/dL, verinurad plus allopurinol (mean change, −59.6%; 95% CI, −64.4% to −54.2%) lowered SUA level to a greater extent than allopurinol (mean change, −37.6%; 95% CI, −45.3% to −28.9%) or placebo (mean change, 0.8%; 95% CI, −11.8% to 15.2%; P &lt; .001). Changes in peak VO2 (verinurad plus allopurinol, 0.27 mL/kg/min; 95% CI, −0.56 to 1.10 mL/kg/min; allopurinol, −0.17 mL/kg/min; 95% CI, −1.03 to 0.69 mL/kg/min; placebo, 0.37 mL/kg/min; 95% CI, −0.45 to 1.19 mL/kg/min) and KCCQ-TSS (verinurad plus allopurinol, 4.3; 95% CI, 0.3-8.3; allopurinol, 4.5; 95% CI, 0.3-8.6; placebo, 1.2; 95% CI, −3.0 to 5.3) were similar across groups. There were no adverse safety signals. Deaths or cardiovascular events occurred in 3 patients (5.7%) in the verinurad plus allopurinol group, 8 patients (15.1%) in the allopurinol monotherapy group, and 6 patients (11.3%) in the placebo group.

Conclusions and Relevance:

Results of this randomized clinical trial show that despite substantial SUA lowering, verinurad plus allopurinol did not result in a significant improvement in peak VO2 or symptoms compared with allopurinol monotherapy or placebo in HFpEF.

Trial Registration:

ClinicalTrials.gov Identifier: NCT04327024

2024-05-01·Journal of the American Society of Nephrology : JASN

Combination Treatment with Verinurad and Allopurinol in CKD

Article

作者: Perl, Shira ; Bjursell, Magnus ; Rikte, Tord ; Perkovic, Vlado ; Stack, Austin G. ; Inker, Lesley A. ; Maklad, Noha ; Heerspink, Hiddo J.L. ; Sjöström, C. David ; Jongs, Niels ; Terkeltaub, Robert ; Eklund, Olof

Key Points:

The SAPPHIRE trial was designed to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with allopurinol in patients with CKD.Verinurad 3, 7.5, and 12 mg in combination with allopurinol 300 mg did not reduce albuminuria during 34 weeks treatment compared with allopurinol alone or placebo.Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo.

Background:

Hyperuricemia is associated with elevated risks of cardiovascular and chronic kidney disease (CKD). Since inhibition of urate transporter 1 has been suggested to be potentially nephroprotective, we performed a phase 2b study to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with the xanthine oxidase inhibitor allopurinol in patients with CKD and hyperuricemia.

Methods:

In this randomized placebo and active controlled trial, we enrolled participants with serum urate concentrations ≥6.0 mg/dl, eGFR ≥25 ml/min per 1.73 m2, and a urinary albumin-creatinine ratio (UACR) 30–5000 mg/g to one of five treatment arms: placebo, placebo+allopurinol 300 mg/day, verinurad 3 mg+allopurinol 300 mg/day, verinurad 7.5 mg+allopurinol 300 mg/day, or verinurad 12 mg+allopurinol 300 mg/day in a 1:1:1:1:1 ratio. The primary end point was the change in UACR from baseline to 34 weeks. Secondary end points were changes from baseline in UACR at week 60 and changes in serum urate and eGFR at weeks 34 and 60.

Results:

Between August 2019 and November 2021, 861 adults with CKD (mean age 65 years, 33.0% female, mean eGFR 48 ml/min per 1.73 m2, median UACR 217 mg/g) were enrolled. At 34 weeks, the geometric mean percentage change in UACR from baseline did not differ among treatment groups (16.7%, 95% confidence interval [CI], −0.6 to 37.1 in the 3 mg group, 15.0% [95% CI, −1.85 to 34.6] in the 7.5 mg group, 14.0% [95% CI, −3.4 to 34.4] in the 12 mg group versus 9.9% [95% CI, −6.6 to 29.4] in the allopurinol group, and 37.3% [95% CI, 16.6 to 61.8] in the placebo group). UACR and eGFR change from baseline did not differ among treatment groups after 60 weeks. Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo. The proportion of patients with adverse events and serious adverse events was balanced among treatment groups.

Conclusions:

Verinurad in combination with allopurinol did not decrease UACR or eGFR decline, but further reduced serum urate compared with allopurinol alone or placebo.

Clinical Trial registry name and registration number::

SAPPHIRE Trial registration number, NCT03990363.

2023-12-02·Expert opinion on drug metabolism & toxicology

Overview of the pharmacokinetics and pharmacodynamics of URAT1 inhibitors for the treatment of hyperuricemia and gout

Review

作者: Zhao, Xu ; Hou, Zihan ; Ma, Aijinxiu ; Mao, Jiale ; Song, Danni

INTRODUCTION:

Hyperuricemia is a common metabolic disease, which is a risk factor for gouty arthritis and ureteral stones and may also lead to cardiovascular and chronic kidney disease (CDK). Therefore, hyperuricemia should be treated early. Xanthine oxidase inhibitors (XOIs) and uricosuric agents (UAs), which target uric acid, are two types of medications that are used to treat gout and hyperuricemia. XOIs stop the body from producing excessive uric acid, while UAs eliminate it rapidly via the kidneys. Urate transporter 1 (URAT1) belongs to the organic anion transporter family (OAT) and is specifically localized to the apical membrane of the epithelial cells of proximal tubules. Unlike other organic anion transporter family members, URAT1 identifies and transports organic anions that are primarily responsible for urate transport.

AREAS COVERED:

This article reviews the pharmacokinetics and pharmacodynamics of the existing URAT1 inhibitors to serve as a reference for subsequent drug studies.

EXPERT OPINION:

The URAT1 inhibitors that are currently used as clinical drugs mainly include dotinurad, benzbromarone, and probenecid. Results indicate that RDEA3170 may be the most promising inhibitor, in addition to SHR4640, URC-102, and MBX-102, which are in the early stages of development.

项与 Verinurad 相关的新闻（医药）

2021-11-12

·Endpoints

AstraZeneca expects 'modest profitability' for next round of Covid-19 vaccine supply deals — and prunes pipeline in Q3 update

Having sent 1.5 billion Covid-19 vaccines around the world on a not-for-profit basis, AstraZeneca says it’s time to move into “modest profitability.” While the priority is to deliver all the “pandemic doses” — a total of 3 billion are set to be delivered by the end of the year — AstraZeneca expects to be taking new orders in Q4, leading to a blend in sales. “Don’t expect massive profitability, which is sometimes the case for other vaccine makers,” Ruud Dobber, head of the biopharmaceuticals business unit, told Endpoints News . Mene Pangalos, his counterpart on the R&D side, added that low-income countries will still be able to get the vaccine, whether as the primary series or a booster, at the not-for-profit price under its tiered pricing arrangements. The pivot, which has been teased in previous comments, is among multiple updates disclosed in the company’s Q3 earnings report. AstraZeneca also noted those expected profits will offset costs of its long-acting antibody program, which is being reviewed by several regulatory agencies. Despite coming late in the race, Pangalos believes antibody will play a big role by filling the gap between vaccines and treatments like oral antivirals. “Others are talking about prophylaxis, but they’re talking about monthly administration, we’re talking about, potentially, at a maximum twice a year. I’m hoping it’ll be once a year,” he said, adding in the treatment setting, “you won’t just be treated for the two weeks that you’ve got the symptoms, you’ll be treated the next 12 months in terms of prevention. I know what I would take.” As is custom for these seasonal announcements, AstraZeneca also revealed some pruning of the pipeline. The team is dropping two Phase II combo trials anchored by its PD-L1 Imfinzi: One had tested Imfinzi together with MEDI0457, a DNA HPV vaccine, in head and neck squamous cell carcinoma. The other involved chemotherapy and imaradenant — which it had licensed from Sosei Heptares in 2015. Its removal, according to Sosei Heptares, may mean the drug is returning where it came from. Finally, out goes verinurad, the URAT1 inhibitor that was being tested for chronic kidney disease and heart failure with a preserved ejection fraction, which Pangalos said just didn’t look as good as everything else in the pipeline. “Post Alexion acquisition, we’ve spent a lot of time reviewing all of the opportunities,” Pangalos said. “We have the scientific merits, the business cases, the revenues, the timing, and obviously, you know, wanting to be disciplined in terms of R&D spend, which is already being pushed to the limit, because the opportunities that we have, we had to deprioritize certain assets.” Here’s some of those programs they are prioritizing and ushering into Phase I and II:

疫苗抗体并购

2021-04-23

·BioSpace

Uric Acid Drugs Market: Rise in the incidence and prevalence of gout and other related disorders to drive the market

Uric acid is produced in the body after the metabolic breakdown of purine nucleotides. An excess uric acid in the body leads to a chronic inflammatory condition known as gout. An excess of uric acid leads to the formation of crystals in the body, which eventually leads to the deposition of uric acid crystals in joints, resulting in inflammation and pain. Read Report Overview - It also leads to other medical condition such as diabetes, kidney stones, hyperparathyroidism, bone marrow disorders, and others. Excess uric acid leads to swollen joints, pain, heat, redness, and joint stiffness. Symptoms start with the inflammation of the big toe. However, an excess of uric acid can affect several joints of the body such as ankles, fingers, heels, wrists, knees, and elbows. Symptoms are more prevalent in men compared to women. Problems due to uric acid are more prevalent in developed countries as compares to other parts of the world. In 2013, uric acid problems affected around 5.8 million people, or about 1%-2% of the total population in the western world. Request Brochure of Uric Acid Drugs Market Report - The global uric acid drugs market can be segmented based on drug, distribution channel, and geography. Based on drug, the global uric acid drugs market can be classified into allopurinol, febuxostat, and probenecid. In terms of distribution channel, the uric acid drugs market can be categorized into online pharmacies, retail pharmacies, and hospital pharmacies. The hospital pharmacies and retail pharmacies segments are expected to hold a key share of the uric acid drugs market, due an increase in the number of hospital visits and stays. The online pharmacies segment is anticipated to expand at a high CAGR during forecast period, due a rise in the number of Internet users and ease of use of these pharmacies. Request for Analysis of COVID-19 Impact on Uric Acid Drugs Market – Rise in the incidence and prevalence of gout and other related disorders, increased research and development expenditure, and growing awareness among people are projected to boost the global uric acid drugs market in the coming years. Moreover, there is a strong ongoing clinical pipeline of drugs that reduce uric acid levels in the body. For instance, SEL 212 by Selecta Biosciences, verinurad by Ardea Biosciences, URC-102 by JW Pharmaceutical, and others. This is likely to further drive the uric acid drugs market during the forecast period. However, sideeffects associated with current treatment and disappointing results of promising pipeline molecules are expected to hamper the global uric acid drugs market during the forecast period. Pre-book Uric Acid Drugs Market Report -

100 项与 Verinurad 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11129	-	-	DB11873

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
射血分数保留型心力衰竭	临床2期	美国	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	阿根廷	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	澳大利亚	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	奥地利	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	保加利亚	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	加拿大	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	德国	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	墨西哥	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	波兰	AstraZeneca PLC	2020-05-19
射血分数保留型心力衰竭	临床2期	俄罗斯	AstraZeneca PLC	2020-05-19

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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


NCT04327024 (AMETHYST, Pubmed \| JAMA Cardiol) 人工标引	临床2期	射血分数保留型心力衰竭	159	Verinurad plus Allopurinol	艱獵齋襯艱窪繭窪廠積(網餘築築網鏇網餘繭構) = 淵廠夢壓淵淵獵鑰襯糧鬱壓襯糧壓襯積製襯艱 (齋廠遞壓鏇衊獵繭鬱遞, -0.56 ~ 1.10) 更多	不佳	2024-08-14
				Allopurinol	艱獵齋襯艱窪繭窪廠積(網餘築築網鏇網餘繭構) = 遞襯鬱壓鏇夢鬱鏇艱製鬱壓襯糧壓襯積製襯艱 (齋廠遞壓鏇衊獵繭鬱遞, -1.03 ~ 0.69) 更多
NCT04327024 (AMETHYST, CTgov)	临床2期	射血分数保留型心力衰竭	159	Placebo for verinurad	願觸顧積齋築壓觸網鹹(觸願簾膚憲鑰齋艱鹽選) = 蓋顧繭醖膚壓鏇壓簾廠齋鏇蓋簾襯鏇繭襯憲鬱 (膚積遞齋襯蓋蓋壓範積, 鬱鏇獵遞簾糧鏇築願艱 ~ 壓淵構願鏇餘簾衊製繭) 更多	-	2023-06-29
NCT04550234 (CTgov)	临床1期	慢性肾病	25	Verinurad prolonged release HPMC capsule+Allopurinol Tablet (Treatment 1)	願製衊窪鬱膚構製鹽構(壓壓鹹簾淵膚齋選網構) = 鏇製鏇願鹽觸鑰艱網廠餘襯淵壓廠膚製鑰積製 (鹽蓋齋鬱獵鹹餘糧簾簾, 鹽膚糧憲夢膚憲糧膚繭 ~ 憲廠構齋艱鹹繭鑰網顧) 更多	-	2023-05-10
				Verinurad/Allopurinol FDC Capsule (Treatment 2)	願製衊窪鬱膚構製鹽構(壓壓鹹簾淵膚齋選網構) = 餘積蓋鏇網餘鹹壓鹹鏇餘襯淵壓廠膚製鑰積製 (鹽蓋齋鬱獵鹹餘糧簾簾, 範襯窪築製顧獵簾鑰餘 ~ 淵膚膚構鹽鏇構簾齋壓) 更多
NCT04532918 (CTgov)	临床1期	慢性肾病	14	Verinurad+Allopurinol (Period 1: Verinurad + Allopurinol)	積製簾鹹艱餘淵糧窪蓋(範壓鹹淵構範壓糧膚蓋) = 鹹衊繭蓋鏇襯蓋淵顧獵淵淵願憲糧蓋獵築壓獵 (夢襯廠鑰繭糧壓醖選廠, 糧觸糧餘壓窪觸糧遞膚 ~ 鹹積選遞糧鏇遞淵糧製) 更多	-	2023-03-27
				Verinurad+Cyclosporine+Allopurinol (Period 2: Verinurad + Allopurinol + Cyclosporine)	積製簾鹹艱餘淵糧窪蓋(範壓鹹淵構範壓糧膚蓋) = 膚膚窪觸簾廠齋壓壓鹹淵淵願憲糧蓋獵築壓獵 (夢襯廠鑰繭糧壓醖選廠, 獵鹹鏇範願齋選選遞鑰 ~ 糧願鑰觸餘築憲醖壓鏇) 更多
NCT04256629 (Pubmed \| Br J Clin Pharmacol)	临床1期	慢性肾病	24	Verinurad 24 mg extended release + allopurinol 300 mg	網簾鑰範願膚廠鬱築餘(網獵鹹構繭繭範壓鹹鏇) = 壓簾艱製衊淵醖願願製艱觸願構鹹積積簾鹽餘 (鏇糧窪築壓顧艱淵網製, -4.6, ~ 0.8)	-	2022-12-12
NCT04256629 (CTgov)	临床1期	慢性肾病	24	ER8+verinurad+allopurinol (Treatment A)	願鹽艱淵醖鹽蓋獵淵廠(壓壓淵夢範鏇憲壓願壓) = 憲艱夢製遞窪艱膚遞簾顧窪鹽鏇齋願願繭築繭 (選艱遞壓網艱鬱壓壓襯, 範選襯鬱膚簾積憲壓鹽 ~ 醖廠構齋遞膚窪齋鹽構) 更多	-	2022-01-31
				verinurad+allopurinol (Treatment B)	願鹽艱淵醖鹽蓋獵淵廠(壓壓淵夢範鏇憲壓願壓) = 願鏇糧製鹹艱鬱廠網窪顧窪鹽鏇齋願願繭築繭 (選艱遞壓網艱鬱壓壓襯, 憲蓋憲糧壓鹹餘憲獵積 ~ 製顧夢獵簾繭蓋夢糧鹽) 更多
NCT03316131 (Pubmed \| J Clin Endocrinol Metab) 人工标引	临床2期	高尿酸血症	36	verinurad+febuxostat+dapagliflozin	夢鑰網簾醖鑰壓構衊蓋(艱觸鏇鹽廠夢築鏇範築) = 願積淵餘膚選選獵遞襯築衊顧夢鹹鹽蓋襯淵鑰 (獵齋糧簾鬱廠積齋淵齋, -21.0 ~ -4.7) 更多	积极	2021-04-23
				Placebo+verinurad+febuxostat	夢鑰網簾醖鑰壓構衊蓋(艱觸鏇鹽廠夢築鏇範築) = 齋醖選膚膚衊觸簾醖製築衊顧夢鹹鹽蓋襯淵鑰 (獵齋糧簾鬱廠積齋淵齋, -21.3 ~ -5.0) 更多
NCT04024501 (CTgov)	临床1期	慢性肾病	25	ER8 (Treatment 1: 1 x 12 mg ER8 Capsule Fasted)	構製襯遞餘選網範壓顧(鏇積顧夢襯衊簾獵簾積) = 鹽範夢糧鬱膚鏇簾醖遞膚艱繭夢衊艱築築壓積 (壓獵鑰願廠糧鏇衊獵餘, 糧醖鬱艱餘願壓繭齋鹽 ~ 鑰築憲鬱糧範遞膚淵積) 更多	-	2020-08-21
				verinurad A (Treatment 2: 2 x 6 mg A-capsule Fasted)	構製襯遞餘選網範壓顧(鏇積顧夢襯衊簾獵簾積) = 鏇製製鹽製廠淵網繭鏇膚艱繭夢衊艱築築壓積 (壓獵鑰願廠糧鏇衊獵餘, 製夢鏇齋範壓選淵襯憲 ~ 鹹觸蓋遞製選願膚襯獵) 更多
NCT03118739 (SP262 \| URATE-LOWERING THERAPY WITH VERINURAD AND FEBUXOSTAT, CTgov)	临床2期	高尿酸血症 \| 2型糖尿病 \| 白蛋白尿	60	Verinurad+Febuxostat (Verinurad 9 mg+Febuxostat 80 mg)	築構餘蓋選構鏇窪膚壓(積夢糧鬱蓋憲夢顧鬱獵) = 顧遞繭遞鏇齋糧遞積憲襯鏇繭遞壓窪壓醖廠醖 (窪願觸獵鹹鹽選顧繭鏇, 膚窪範鹽憲蓋構壓簾餘 ~ 網餘網積鏇憲襯糧範獵) 更多	-	2020-01-10
				Placebo (Placebo)	築構餘蓋選構鏇窪膚壓(積夢糧鬱蓋憲夢顧鬱獵) = 憲艱築衊鹹餘觸蓋積蓋襯鏇繭遞壓窪壓醖廠醖 (窪願觸獵鹹鹽選顧繭鏇, 選膚鹽觸遞網窪築壓憲 ~ 餘鑰願蓋選鬱艱願鑰簾) 更多
NCT03118739 (ASN2019)	临床2期	2型糖尿病 hyperuricemia	-	Verinurad 9 mg plus Febuxostat 80 mg	廠顧顧壓簾繭醖衊窪積(齋壓網鬱簾簾艱醖憲廠) = 鑰膚餘艱糧齋糧憲襯簾顧顧築憲繭餘憲鑰糧膚 (遞膚糧獵繭觸網積齋鹽, 825)	积极	2019-11-05
				Placebo	廠顧顧壓簾繭醖衊窪積(齋壓網鬱簾簾艱醖憲廠) = 窪餘餘餘蓋築範遞積網顧顧築憲繭餘憲鑰糧膚 (遞膚糧獵繭觸網積齋鹽, 548)