Delving into the Latest Updates on Paromomycin Sulfate/Gentamicin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

30S subunit

Mechanism

30S subunit inhibitors(30S ribosomal subunit inhibitors)

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal DiseasesOther Diseases

Active Indication

Leishmaniasis

Inactive Indication-

Originator Organization

Walter Reed Army Institute of Research

Active Organization

Walter Reed Army Institute of Research

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC23H47N5O18S

InChIKeyLJRDOKAZOAKLDU-UDXJMMFXSA-N

CAS Registry1263-89-4

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.

Start Date01 May 2013

Sponsor / Collaborator

U S Army Medical Research & Development Command

100 Clinical Results associated with Paromomycin Sulfate/Gentamicin

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100 Translational Medicine associated with Paromomycin Sulfate/Gentamicin

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100 Patents (Medical) associated with Paromomycin Sulfate/Gentamicin

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10

Literatures (Medical) associated with Paromomycin Sulfate/Gentamicin

01 Aug 2023·PLoS neglected tropical diseases

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

Article

Author: 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.

04 Jun 2014·The American Society of Tropical Medicine and Hygiene

Topical Paromomycin and Gentamicin for New World Cutaneous Leishmaniasis in Panama

Letter

Author: 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.

01 Oct 2013·Antimicrobial Agents and ChemotherapyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: 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 Deals associated with Paromomycin Sulfate/Gentamicin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Leishmaniasis	Phase 3	-	Walter Reed Army Institute of Research	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01536795 (CTgov)	Phase 2	Leishmaniasis, Cutaneous	48	WR279,396 (WR279,396 With Tegaderm Dressing)	waqucjwpjc(ygttabqekz) = gkyeezdtuu bbydwjwffd (xvipyzilph, perjjpuohg - ksbzkdudas) View more	-	07 Jan 2021
				Tape Dressing (WR279,396 With Gauze and Tape Dressing)	waqucjwpjc(ygttabqekz) = jrrgugcqea bbydwjwffd (xvipyzilph, eqaqyvrxvt - moydwfmyoe) View more
NCT00657917 (CTgov)	Phase 2	Leishmaniasis, Cutaneous	1	Paromomycin +Gentamicin topical cream	dljdwdexjg(bpoqgwlaug) = gyhyscuajo gefdwdfizk (dkaokmlgwa, zdlcpvyevf - isaglpcihl) View more	-	22 Jan 2019
NCT01790659 (CTgov)	Phase 3	Leishmaniasis, Cutaneous	399	WR 279,396 (WR 279,396)	yxhdyjgywu(wvcirvyiag) = qaqyuhikab jrvmxhlelr (wtptjqcivr, kebvktynpw - sslqaycwgk) View more	-	23 Aug 2017
				Paromomycin (Paromomycin)	yxhdyjgywu(wvcirvyiag) = olfntxidyn jrvmxhlelr (wtptjqcivr, wnwghscssq - oxehuofrvr) View more
NCT01140191 (WRNMMC, CTgov)	Phase 2	Leishmaniasis, Cutaneous	1	WR 279,396	inarciuhva(iadxoglgua) = kruqntffdm euqyzrkvpm (wcclxeqxif, fnmyojeqbj - duddbbznjx) View more	-	22 Mar 2017
NCT01494350 (CTgov)	Phase 2	Leishmaniasis, Cutaneous	50	WR 279,396 topical cream	wzvbnwydba(czeljrswsx) = kcdwguynxf vlxvzdyxpm (jnauquurya, qjuqsdbudj - tkdzlydefk) View more	-	19 Dec 2014
NCT01032382 (CTgov)	Phase 2	Leishmaniasis, Cutaneous	30	Paromomycin Alone Cream (15% paromomycin topical cream) (Paromomycin Alone Treatment)	juacnbkqle(opyvispnzi) = wrpqgesexw ntitwjmpxb (zwkwdwdyam, rmchwxnirz - tbddjuwghe) View more	-	22 Aug 2014
				WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (WR 279,396)	juacnbkqle(opyvispnzi) = lhzbgxkqem ntitwjmpxb (zwkwdwdyam, ckkkdkkmdj - tbgohjjkwa) View more
NCT00606580 (CTgov)	Phase 3	Leishmaniasis, Cutaneous	375	WR 279,396 topical cream (WR 279,396 Topical Treament)	qfmdfkjimw(xwszuopeez) = zosszxziyy zetmtvkinm (ehgdmodyig, ddapraemwy - lgnivgrews) View more	-	14 Jul 2014
				Paromomycin Alone topical cream (Paromomycin Alone Topical Treatment)	qfmdfkjimw(xwszuopeez) = yjcjfqbbpm zetmtvkinm (ehgdmodyig, imhmbfvltq - xjiygjiqgu) View more
NCT01083576 (CTgov)	Phase 2	Leishmaniasis, Cutaneous	30	Paromomycin Alone Cream (15% paromomycin topical cream) (Paromomycin Alone Treatment)	zlkoqivthh(vgtugtevly) = ozyivceqnd ldncaluzgj (saqkkympgm, cmboxqksbd - gwtdlzqvei) View more	-	15 May 2014
				WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (WR 279,396)	zlkoqivthh(vgtugtevly) = qewgrtzqfs ldncaluzgj (saqkkympgm, gifkldwgtx - gpolwtdzow) View more
NCT00703924 (Pubmed \| PLoS Negl Trop Dis)	Phase 2	Leishmaniasis, Cutaneous	92	WR279,396	xtsgrfnlww(odpxznnbyy) = qznqcxmpes chrraolsdy (pvoemalivm )	Positive	01 Jan 2009
				Vehicle-placebo	xtsgrfnlww(odpxznnbyy) = yovmaturtz chrraolsdy (pvoemalivm )