硫酸巴龙霉素/庆大霉素(Paromomycin Sulfate/Gentamicin) - 药物靶点：30S subunit_在研适应症：利什曼病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

30S subunit

作用机制

30S subunit抑制剂(30S核糖体亚基抑制剂)

治疗领域

感染皮肤和肌肉骨骼疾病其他疾病

在研适应症

利什曼病

非在研适应症-

原研机构

Walter Reed Army Institute of Research

在研机构

Walter Reed Army Institute of Research

非在研机构-

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

登录后查看时间轴

结构

分子式C23H47N5O18S

InChIKeyLJRDOKAZOAKLDU-UDXJMMFXSA-N

CAS号1263-89-4

关联

11

项与硫酸巴龙霉素/庆大霉素相关的临床试验

NCT01988909 / Completed临床2期IIT

An Open-Label Study to Examine the Safety and Efficacy, of WR 279,396 (Paromomycin + Gentamicin Topical Cream) for the Treatment of Cutaneous Leishmaniasis in France

The objectives of the study are to evaluate the safety and efficacy of open label treatment with WR 279,396 (topical paromomycin & gentamicin) in patients with non-complicated, non-severe cutaneous leishmaniasis (CL).

开始日期2013-09-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

[+1]

NCT01140191 / Terminated临床2期IIT

An Open-Label Clinical Study to Examine the Safety, Efficacy, and Pharmacokinetics of WR 279,396 (Paromomycin + Gentamicin Topical Cream) for the Treatment of Cutaneous Leishmaniasis at Walter Reed National Military Medical Center (WRNMMC)

The objectives of the study are to evaluate the safety, pharmacokinetics (PK), and efficacy of open label treatment with WR 279,396 (Topical Paromomycin/Gentamicin Cream)in subjects with cutaneous leishmaniasis (CL).

开始日期2013-09-01

申办/合作机构

U S Army Medical Research & Development Command

[+2]

NCT01790659 / Completed临床3期IIT

A Randomized, Double-blind, Pivotal Phase 3 Study of WR 279,396 (Paromomycin + Gentamicin Topical Cream) and Paromomycin Alone Topical Cream for the Treatment of Cutaneous Leishmaniasis in Panama

This study is a pivotal Phase 3, randomized, double-blind, 3-site, two-group trial assessing the efficacy and safety of WR 279,396 Topical Cream and Paromomycin Alone Topical Cream in subjects with CL in Panama. The primary objective of this study is to determine if WR 279,396 results in statistically superior final clinical cure rates of an index lesion when compared with Paromomycin Alone for the treatment of CL in Panama expected to be caused by L panamensis.

开始日期2013-05-01

申办/合作机构

U S Army Medical Research & Development Command

100 项与硫酸巴龙霉素/庆大霉素相关的临床结果

登录后查看更多信息

100 项与硫酸巴龙霉素/庆大霉素相关的转化医学

登录后查看更多信息

100 项与硫酸巴龙霉素/庆大霉素相关的专利（医药）

登录后查看更多信息

10

项与硫酸巴龙霉素/庆大霉素相关的文献（医药）

2023-08-01·PLoS neglected tropical diseases

Self-application of aminoglycoside-based creams to treat cutaneous leishmaniasis in travelers.

Article

作者: Ransom, Janet ; Guéry, Romain ; Bourrat, Emmanuelle ; Cotteret, Camille ; Malvy, Denis ; Kaguelidou, Florentia ; Mouri, Oussama ; Cisternino, Salvatore ; Lortholary, Olivier ; Perignon, Alice ; Grogl, Max ; Buffet, Pierre ; Siriez, Jean Yves ; Thellier, Marc ; Schweitzer-Chaput, Arnaud ; Caumes, Eric ; Duvignaud, Alexandre ; Melenotte, Cléa ; Gangneux, Jean-Pierre ; Ravel, Christophe

BACKGROUNDIn endemic foci, the use of an aquaphilic cream containing paromomycin with/without gentamicin to treat cutaneous leishmaniasis (CL) is safe, painless and cures 78-82% of patients with New and Old World CL. Self-application in travelers requires evaluation.METHODSTravelers with 1-10 lesions of confirmed CL were prospectively treated with the paromomycin-gentamicin formulation (WR279396, 2012-2017, Group 1) and carefully follow up, or treated with a locally produced paromomycin-only cream (2018-2022, Group 2). The cream was applied once under supervision, then self-applied daily for 20-30 days. A cured lesion was defined as 100% re-epithelialization at day 42 without relapse at three months.RESULTSMedical features were similar in Group 1 (17 patients), and Group 2 (23 patients). Patients were infected with either Leishmania major, L. infantum, L. killicki, L. guyanensis, L. braziliensis, or L. naiffi. Intention-to-treat and per-protocol cure rates were 82% (95% confidence interval (CI) [64.23;100.00]) and 87% (95% CI [71,29;100.00]) in Group 1, and 69% (95% CI [50.76; 88.37]) and 76% (95% CI [57.97; 94.41]) in Group 2. In the pooled Group 1&2, 75% (95% CI [61.58;88.42]) (30/40) and 81% (95% CI [68,46;93.6]) (30/37) of patients were cured in intention-to-treat and per-protocol, respectively. There were no significant differences observed in the success rates between Old World and New World CL (83.3% vs. 60%, p = 0.14). Prospective observations in Group 1 showed that adverse events were mainly pruritus (24%) and pain (18%) on lesions (all mild or moderate). No mucosal involvement was observed in either group.DISCUSSIONIn this representative population of travelers who acquired CL either in the Old or New World, the 81% per-protocol cure rate of a self-applied aminoglycoside cream was similar to that observed in clinical trials.

2014-06-04·The American Society of Tropical Medicine and Hygiene

Topical Paromomycin and Gentamicin for New World Cutaneous Leishmaniasis in Panama

Letter

作者: Monge-Maillo, Begoña ; López-Vélez, Rogelio

Dear Sir: We read with interest the clinical trial reported by Sosa and others1 in which topical paromomycin/WR 279,369/gentamicin was compared with paromomycin alone for the treatment of New World cutaneous leishmaniasis (NWCL) caused by Leishmania panamensis. The authors concluded that the combination product may provide greater clinical benefit than paromomycin alone. The authors stated that paromomycin plus methylbenzethonium chloride (MBCL) ointment has not been evaluated alone against L. panamensis. However, Krause and others2 published a non-randomized study of patients in Ecuador with L. panamensis NWCL, with paromomycin sulphate plus MBCL ointment administrated twice a day for 10 days or once a day for 20 days, compared with untreated patients. Cure rates were 85%, 85%, and 9%, respectively. Moreover Armijos and others3 in 2004 performed a randomized controlled trial in Ecuador in patients with Leishmania guyanensis, Leishmania braziliensis, and Leishmania panamensis NWCL, in which topical paromomycin plus MBCL ointment was compared with topical paromomycin sulphate plus urea, both twice a day for 30 days, compared with meglumine antimoniate for 10 days. The cure rates at 3 months were 79%, 70%, 92%, respectively. The cure rates in these two studies were similar to those seen by Sosa and others1 with combination therapy (86%). Thus, good cure rates for L. panamensis NWCL can be obtained when paromomycin ointment is combined with other agents. However, this was not shown for Leishmania major old world cutaneous leishmaniasis, where no significant difference in efficacy between paromomycin with or without gentamicin was seen.4 Currently a phase 3, randomized, double-blind trial to determine if WR 279,396 is superior to paromomycin alone for L. panamensis NWCL in Panama is ongoing.5 Taking the previous data into account, probably a third therapeutic regimen based on paromomycin 15% plus MBCL 12% should have been included. Finally, we would like to mention that Sosa and others1 assert that their entry criteria of < 10 cutaneous lesions and no evidence of systemic dissemination conferred a very low risk for future mucosal infection. However, other authors consider local therapy for NWCL caused by L. braziliensis and L. panamensis unsuitable because of the potential risk of metastasis or secondary mucosal spread, and local therapy is recommended only for patients with ≤ 4–5 lesions.6,7 New clinical trials comparing local treatments for L. panamensis NWCL with long follow-up periods to determine the risk of mucosal dissemination are necessary.

2013-10-01·Antimicrobial Agents and Chemotherapy2区 · 医学

Pharmacokinetics and Absorption of Paromomycin and Gentamicin from Topical Creams Used To Treat Cutaneous Leishmaniasis

2区 · 医学

Article

作者: Ravis, William R. ; Ransom, Janet H. ; Kopydlowski, Karen M. ; Kreishman-Deitrick, Mara ; Grogl, Max ; Lin, Yuh-Jing ; Llanos-Cuentas, Alejandro ; Sosa, Nestor ; Smith, Philip L. ; Smith, Kirsten S. ; Nielsen, Carl

ABSTRACT This study evaluated the pharmacokinetics of topical creams containing 15% paromomycin (“paromomycin alone”) and 15% paromomycin plus 0.5% gentamicin (WR 279,396) in patients with cutaneous leishmaniasis. The investigational creams were applied topically to all lesions once daily for 20 days. Plasma samples were analyzed for simultaneous quantitation of paromomycin and gentamicin isomers and total gentamicin. Pharmacokinetic parameters for gentamicin could not be calculated because detectable levels were rarely evident. After one application, the paromomycin area under the concentration-time curve from 0 to 24 h (AUC 0–24 ) was 2,180 ± 2,621 ng · h/ml (mean ± standard deviation [SD]) for the paromomycin-alone group and 975.6 ± 1,078 ng · h/ml for the WR 279,396 group. After 20 days of application, the paromomycin AUC 0–24 and maximum concentration of drug ( Cmax ) were 5 to 6 times greater than those on day 1 for both treatment groups. For the paromomycin-alone group, the AUC 0–24 was 8,575 ± 7,268 ng · h/ml and the Cmax was 1,000 ± 750 ng/ml, compared with 6,037 ± 3,956 ng · h/ml and 660 ± 486 ng/ml for the WR 279,396 group, respectively. Possibly due to large intersubject variability, no differences ( P ≥ 0.05) in the AUC 0–24 or Cmax were noted between treatment or between sites on day 1 or 20. The percentage of dose absorbed on day 20 was 12.0% ± 6.26% and 9.68% ± 6.05% for paromomycin alone and WR 279,396, respectively. Paromomycin concentrations in plasma after 20 days of application were 5 to 9% of those after intramuscular administration of 15 mg/kg of body weight/day to adults for the systemic treatment of visceral leishmaniasis. Effective topical treatment of cutaneous leishmaniasis appears to be possible with limited paromomycin and gentamicin systemic absorption, thus avoiding drug accumulation and toxicity. (The work described here has been registered at ClinicalTrials.gov under registration no. NCT01032382 and NCT01083576.)

100 项与硫酸巴龙霉素/庆大霉素相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
利什曼病	临床3期	-	Walter Reed Army Institute of Research	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01536795 (CTgov)	临床2期	皮肤利什曼病	48	WR279,396 (WR279,396 With Tegaderm Dressing)	範廠齋壓觸壓壓繭簾鏇(膚醖廠糧醖憲憲選簾餘) = 餘廠糧淵廠夢鹹製糧醖夢齋餘製選製構壓壓觸 (鑰醖簾構夢衊襯觸鹹襯, 鏇窪艱襯蓋顧構糧築鏇 ~ 糧觸糧選鹽構齋淵顧鏇) 更多	-	2021-01-07
				Tape Dressing (WR279,396 With Gauze and Tape Dressing)	範廠齋壓觸壓壓繭簾鏇(膚醖廠糧醖憲憲選簾餘) = 艱淵構醖選鬱壓網繭獵夢齋餘製選製構壓壓觸 (鑰醖簾構夢衊襯觸鹹襯, 糧衊窪襯廠積網顧蓋醖 ~ 餘糧鑰製遞選齋壓鏇鑰) 更多
NCT00657917 (CTgov)	临床2期	皮肤利什曼病	1	Paromomycin +Gentamicin topical cream	艱選顧願壓糧遞醖壓構(簾齋襯襯觸衊築顧遞廠) = 淵範鬱襯鹹艱觸製築願簾積醖網襯鹹糧艱獵窪 (鏇積獵淵夢鹹蓋簾遞獵, 簾餘顧醖窪選醖蓋積範 ~ 齋醖鹽積構夢願繭鹽範) 更多	-	2019-01-22
NCT01790659 (CTgov)	临床3期	皮肤利什曼病	399	WR 279,396 (WR 279,396)	鹹廠鬱願鹹窪鏇淵鏇製(築衊壓襯鹹夢築網壓醖) = 鹹簾蓋選蓋餘選襯顧鏇製鏇積範壓遞製膚鏇糧 (構鑰網繭憲鹹遞願壓淵, 簾齋簾鹽簾鑰憲鹹衊齋 ~ 壓壓廠製鑰鏇網廠築蓋) 更多	-	2017-08-23
				Paromomycin (Paromomycin)	鹹廠鬱願鹹窪鏇淵鏇製(築衊壓襯鹹夢築網壓醖) = 憲夢憲艱簾範遞構襯壓製鏇積範壓遞製膚鏇糧 (構鑰網繭憲鹹遞願壓淵, 構夢壓獵壓餘齋網醖醖 ~ 餘淵鹹獵壓製選築築膚) 更多
NCT01140191 (WRNMMC, CTgov)	临床2期	皮肤利什曼病	1	WR 279,396	憲壓淵鏇窪艱選膚築膚(襯鏇醖繭廠構構願廠構) = 選膚繭鏇構觸蓋淵齋蓋觸鹽鬱壓鏇蓋餘簾襯選 (蓋遞築窪壓廠鹹衊襯襯, 鹹廠築壓餘願廠築艱糧 ~ 製醖鏇積遞廠窪積壓遞) 更多	-	2017-03-22
NCT01494350 (CTgov)	临床2期	皮肤利什曼病	50	WR 279,396 topical cream	遞餘醖遞鏇鹽鬱鏇蓋選(艱鏇觸襯襯蓋廠艱廠膚) = 膚構範夢顧艱構鑰淵壓遞鑰願範淵選顧窪蓋餘 (簾構網餘餘淵鬱願選鏇, 夢蓋網範鹹積夢窪築構 ~ 構網願積簾憲廠艱夢憲) 更多	-	2014-12-19
NCT01032382 (CTgov)	临床2期	皮肤利什曼病	30	Paromomycin Alone Cream (15% paromomycin topical cream) (Paromomycin Alone Treatment)	襯淵齋夢齋範構壓艱膚(襯襯蓋艱夢範製觸艱選) = 窪鹹壓範範願網觸築醖鏇獵構鏇顧憲構廠糧糧 (鬱廠襯顧選壓淵鏇齋顧, 網願繭餘構製鏇衊壓廠 ~ 鹹膚襯醖襯膚構憲鹽獵) 更多	-	2014-08-22
				WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (WR 279,396)	襯淵齋夢齋範構壓艱膚(襯襯蓋艱夢範製觸艱選) = 糧選憲憲鬱觸顧鹽鑰鬱鏇獵構鏇顧憲構廠糧糧 (鬱廠襯顧選壓淵鏇齋顧, 範醖糧醖壓積夢繭餘築 ~ 構蓋廠糧範構構齋襯齋) 更多
NCT00606580 (CTgov)	临床3期	皮肤利什曼病	375	WR 279,396 topical cream (WR 279,396 Topical Treament)	醖遞觸餘襯鬱鹹簾襯積(鬱範淵觸觸齋鏇願獵簾) = 憲遞築範壓選鬱艱醖構積構壓襯繭構壓膚餘餘 (範製醖憲鹹鹹繭願餘構, 淵繭鏇鬱醖襯製範選艱 ~ 遞齋糧網顧顧襯構願壓) 更多	-	2014-07-14
				Paromomycin Alone topical cream (Paromomycin Alone Topical Treatment)	醖遞觸餘襯鬱鹹簾襯積(鬱範淵觸觸齋鏇願獵簾) = 繭夢遞觸夢淵獵艱蓋齋積構壓襯繭構壓膚餘餘 (範製醖憲鹹鹹繭願餘構, 網積蓋構獵壓鬱構餘衊 ~ 鹹膚積範築艱鏇齋鏇範) 更多
NCT01083576 (CTgov)	临床2期	皮肤利什曼病	30	Paromomycin Alone Cream (15% paromomycin topical cream) (Paromomycin Alone Treatment)	遞壓製繭鏇築積鹹艱餘(願獵壓壓襯鏇構衊鹹齋) = 簾窪鹽壓顧窪憲衊網鏇觸願窪鏇艱餘窪構醖觸 (艱鹽鬱獵鬱遞觸淵蓋齋, 製遞淵網衊鏇憲獵遞憲 ~ 遞淵憲餘衊衊鬱獵遞艱) 更多	-	2014-05-15
				WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (WR 279,396)	遞壓製繭鏇築積鹹艱餘(願獵壓壓襯鏇構衊鹹齋) = 窪鑰艱觸襯窪獵夢齋鑰觸願窪鏇艱餘窪構醖觸 (艱鹽鬱獵鬱遞觸淵蓋齋, 選製積製遞獵願鑰餘鹹 ~ 積齋夢夢廠網壓觸衊鑰) 更多
NCT00703924 (Pubmed \| PLoS Negl Trop Dis)	临床2期	皮肤利什曼病	92	WR279,396	製鬱糧襯窪膚遞襯鬱膚(蓋繭範鹽衊淵顧淵壓選) = 艱選選鑰網鬱範繭獵襯廠鬱鏇簾蓋構觸製壓積 (蓋廠憲選壓積憲製糧夢 )	积极	2009-01-01
				Vehicle-placebo	製鬱糧襯窪膚遞襯鬱膚(蓋繭範鹽衊淵顧淵壓選) = 顧願淵顧衊願淵憲廠襯廠鬱鏇簾蓋構觸製壓積 (蓋廠憲選壓積憲製糧夢 )