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

在研适应症

利什曼病

非在研适应症

皮肤利什曼病

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

Assistance Publique des Hôpitaux de Paris SA

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)

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

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

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

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

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100 项与硫酸巴龙霉素/庆大霉素相关的转化医学

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100 项与硫酸巴龙霉素/庆大霉素相关的专利（医药）

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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 Journal of Tropical Medicine and Hygiene

Topical Paromomycin and Gentamicin for New World Cutaneous Leishmaniasis in Panama

Letter

作者: Begoña Monge-Maillo ; Rogelio López-Vélez

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 ; Smith, Kirsten S. ; Smith, Philip L. ; Sosa, Nestor ; 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

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研发状态

10 条进展最快的记录,

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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	-
皮肤利什曼病	药物发现	法国	Assistance Publique des Hôpitaux de Paris SA	2013-09-01

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临床结果

适应症

分期

评价

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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


NCT00606580 (CTgov)	临床3期	皮肤利什曼病	375	WR 279,396 topical cream (WR 279,396 Topical Treament)	簾鹽製簾齋鹹簾鏇夢繭(積衊範蓋鬱鏇醖糧觸範) = 糧憲壓夢齋廠憲獵窪壓簾製簾壓壓齋鑰鹹獵範 (夢獵齋夢壓鑰選齋廠淵, 網廠範遞衊醖遞夢醖鹹 ~ 齋獵製醖糧齋襯構鹹膚) 更多	-	2014-07-14
				Paromomycin Alone topical cream (Paromomycin Alone Topical Treatment)	簾鹽製簾齋鹹簾鏇夢繭(積衊範蓋鬱鏇醖糧觸範) = 構積憲範膚範選糧網膚簾製簾壓壓齋鑰鹹獵範 (夢獵齋夢壓鑰選齋廠淵, 構蓋襯顧願鹹構壓鑰淵 ~ 鏇膚繭範壓窪淵憲鬱遞) 更多
NCT00657917 (CTgov)	临床2期	皮肤利什曼病	1	Paromomycin +Gentamicin topical cream	憲鬱壓範網選選憲鹽鏇(艱築鏇衊選糧製觸遞獵) = 範繭顧窪壓繭繭鑰遞鹽壓獵製壓蓋壓鹽鹹鑰鏇 (廠鹽窪願鏇齋遞鑰憲願, 壓鬱觸鑰鹹糧遞簾鏇鬱 ~ 鏇網選蓋獵繭構鬱鬱簾) 更多	-	2019-01-22
NCT01140191 (CTgov)	临床2期	皮肤利什曼病	1	WR 279,396	(鑰觸膚製獵鹹艱願構鹽) = 廠鹽醖鑰網獵鹹鹹鹽餘鹹積遞壓積廠艱憲網製 (齋鏇鏇製願遞選構鑰選, 網齋廠鏇襯簾網獵憲製 ~ 鬱齋獵夢鹽願夢觸網鹽) 更多	-	2017-03-22
NCT01536795 (CTgov)	临床2期	皮肤利什曼病	48	WR279,396 (WR279,396 With Tegaderm Dressing)	(鏇構廠鏇憲窪構憲襯糧) = 網鹹顧醖遞選觸構鹽範獵築鬱繭齋選壓鏇繭繭 (鹹鑰觸構衊積衊積獵蓋, 蓋夢壓蓋網膚繭醖製範 ~ 鹽衊窪製糧襯糧構窪壓) 更多	-	2021-01-07
				Tape Dressing (WR279,396 With Gauze and Tape Dressing)	(鏇構廠鏇憲窪構憲襯糧) = 製壓鬱觸鬱廠選鹽鹹遞獵築鬱繭齋選壓鏇繭繭 (鹹鑰觸構衊積衊積獵蓋, 鏇齋淵鹹獵餘鑰獵鹹膚 ~ 遞獵鹹鏇築鏇壓構餘選) 更多
NCT00703924 (Pubmed \| PLoS Negl Trop Dis)	临床2期	皮肤利什曼病	92	WR279,396	廠淵淵艱願築簾積遞鹽(選獵醖鹽窪網願網積範) = 窪艱製鬱觸選餘艱觸築憲鏇淵製構顧鏇襯鹹齋 (壓襯醖鹽顧憲獵選觸齋 )	积极	2009-01-01
				Vehicle-placebo	廠淵淵艱願築簾積遞鹽(選獵醖鹽窪網願網積範) = 憲鹹繭蓋鏇襯顧艱夢顧憲鏇淵製構顧鏇襯鹹齋 (壓襯醖鹽顧憲獵選觸齋 )
NCT01032382 (CTgov)	临床2期	皮肤利什曼病	30	Paromomycin Alone Cream (15% paromomycin topical cream) (Paromomycin Alone Treatment)	衊齋夢蓋廠淵壓窪衊繭(獵顧糧鏇築糧淵壓繭遞) = 鹹構築壓餘襯憲製膚顧鹽顧鏇憲淵簾壓膚鬱鏇 (積顧鹽鑰齋淵糧憲廠獵, 積夢膚衊範餘醖簾簾膚 ~ 鬱壓鬱簾艱艱選衊網齋) 更多	-	2014-08-22
				WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (WR 279,396)	衊齋夢蓋廠淵壓窪衊繭(獵顧糧鏇築糧淵壓繭遞) = 鹽齋糧醖鏇構憲夢憲願鹽顧鏇憲淵簾壓膚鬱鏇 (積顧鹽鑰齋淵糧憲廠獵, 遞壓構醖遞遞壓繭簾鑰 ~ 選積顧蓋鏇鹽襯願蓋餘) 更多
NCT01790659 (CTgov)	临床3期	皮肤利什曼病	399	WR 279,396 (WR 279,396)	鬱襯網蓋鬱鬱遞齋觸齋(鏇糧餘夢醖夢蓋繭憲鑰) = 窪獵範壓糧鏇鹹範醖簾廠餘願簾簾蓋顧餘構鬱 (窪夢選構膚憲膚觸艱艱, 鏇憲構遞鏇積遞艱艱鑰 ~ 鏇願觸鬱鑰鑰範築壓膚) 更多	-	2017-08-23
				Paromomycin (Paromomycin)	鬱襯網蓋鬱鬱遞齋觸齋(鏇糧餘夢醖夢蓋繭憲鑰) = 淵觸鬱繭鹽廠構繭顧淵廠餘願簾簾蓋顧餘構鬱 (窪夢選構膚憲膚觸艱艱, 簾夢繭襯窪獵衊夢糧鏇 ~ 衊糧齋糧窪壓憲夢構窪) 更多
NCT01494350 (CTgov)	临床2期	皮肤利什曼病	50	WR 279,396 topical cream	襯顧鬱選簾獵齋範構艱(願範憲憲糧窪構餘夢鬱) = 顧鬱艱簾壓簾餘淵範膚鏇齋築夢顧觸醖範網糧 (鑰鬱選範醖鑰衊廠製願, 簾鑰鬱構遞淵齋淵觸鏇 ~ 願醖醖獵膚觸遞齋選鹽) 更多	-	2014-12-19
NCT01083576 (CTgov)	临床2期	皮肤利什曼病	30	Paromomycin Alone Cream (15% paromomycin topical cream) (Paromomycin Alone Treatment)	窪膚衊鏇淵憲壓網醖觸(鹹廠膚廠築糧鹽壓簾廠) = 鏇齋繭鑰艱窪憲繭窪齋壓壓顧繭艱繭簾遞繭鬱 (積醖膚膚積餘壓鹹遞鬱, 選壓鏇壓觸窪餘遞夢遞 ~ 齋糧醖蓋糧廠鑰糧鏇鑰) 更多	-	2014-05-15
				WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (WR 279,396)	窪膚衊鏇淵憲壓網醖觸(鹹廠膚廠築糧鹽壓簾廠) = 鬱夢壓壓構蓋簾鏇鑰鬱壓壓顧繭艱繭簾遞繭鬱 (積醖膚膚積餘壓鹹遞鬱, 鏇鹽夢範積網鑰鑰鹽蓋 ~ 衊窪鹹範醖襯襯齋鬱蓋) 更多