A Randomized Controlled Trial of Alternating Irrigation of Vancomycin Hydrochloride and Tobramycin Sulfate in Patients Undergoing Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection (PJI) of the Hip or Knee

Study Type: A multi-site, parallel group, randomized trial.
Study Objectives: The objective is to evaluate safety and determine preliminary efficacy of VT-X7 (Vancomycin and Tobramycin Exchanged over 7 Days). Efficacy is evaluated as superiority of the Experimental Arm in a composite endpoint of Overall Success at 90 days, consisting of a revision prosthesis implanted at Stage 2, patient survival, absence of reoperation and absence of periprosthetic joint infection (PJI). Secondary objectives are to evaluate superiority at 365 days in a composite endpoint of Overall Success, and in separate secondary endpoints for quality of life and patient survival. The exploratory objective is to compare Experimental and Control Arms in exploratory endpoints.
Follow-up: Patients will be evaluated at 90-, 180-, and 365-day follow-up visits.

Start Date01 Nov 2021

Sponsor / Collaborator

Osteal Therapeutics, Inc.

NCT03721328 / CompletedPhase 2

A Phase 2 Multicenter Feasibility Trial to Evaluate Safety and Efficacy in Patients Treated for Hip or Knee Prosthetic Joint Infection (PJI) With Alternating Irrigation of Vancomycin Hydrochloride (HCl) and Tobramycin Sulfate in Two-Stage Exchange Arthroplasty

Study Type
Prospective, single-arm, open-label, multicenter (3 to 5 sites), interventional trial.
Primary Study Objective
The objective of the study is to determine the safety profile of local antibiotic irrigation for the treatment of PJI.
Primary Outcome Measure
The overall safety profile is characterized by assessing the incidence of adverse events (AEs), serious adverse events (SAEs), suspected adverse reactions, adverse reactions, and unexpected adverse reactions.
Follow-up
Patients will be assessed for all measures at 3 weeks, 6 weeks, 12 weeks, and 12 months from initial surgery.

Start Date26 Oct 2018

Sponsor / Collaborator

Osteal Therapeutics, Inc.

NCT03066453 / TerminatedPhase 3IIT

Evaluation of an Antibiotic Treatment With 14 Days of Intravenous Tobramycin Versus the Same Antibiotic Associated With 5 Days of Intravenous Tobramycin Followed by Tobramycin Aerosol for 9 Days in Cystic Fibrosis.

The aim of this study is to investigate the efficacy of antibiotic therapy with any antibiotic (IV) and IV (Nebcin®) tobramycin for 5 days followed by Solution for nebuliser inhalation (Tobi®) for 9 days and antibiotic cures using 14 days of tobramycin IV. In the case of positive results, the reduction of the duration of IV treatment of tobramycin from 14 days to 5 days would limit the risk of toxicity.

Start Date13 Jun 2017

Sponsor / Collaborator

Centre Hospitalier Universitaire de Lille

100 Clinical Results associated with Tobramycin Sulfate

100 Translational Medicine associated with Tobramycin Sulfate

100 Patents (Medical) associated with Tobramycin Sulfate

161

Literatures (Medical) associated with Tobramycin Sulfate

01 Jan 2021·Journal of advanced pharmaceutical technology & research

Investigating nanostructured liquid crystalline particles as prospective ocular delivery vehicle for tobramycin sulfate: Ex vivo and in vivo studies

Article

Author: Kaul, Shreya ; Nagaich, Upendra ; Verma, Navneet

Tobramycin remains the anchor drug for bacterial keratitis treatment and management; however, unlike other aminoglycosides, it does not pass through the gastrointestinal tract. The aim of the current investigation was to formulate tobramycin-loaded nanostructured liquid crystalline particles as an ophthalmic drug delivery system to ameliorate its preocular residence duration and ophthalmic bioavailability. Tobramycin cubosomes were fabricated by liquid-lipid monoolein, water, and poloxamer 407 as a stabilizer. Corneal penetration studies exhibited that the apparent permeation coefficient of tobramycin cubosomes was nearly 3.6-fold greater than marketed tobramycin eye drops. Ocular in vivo analysis performed in rabbits' eyes manifested that the intensity of bacterial keratitis was reduced on day 3, and on day 5, the manifestations were considerably mitigated with tobramycin cubosomes as compared to marked eye drops. Pharmacokinetic study of rabbit aqueous humor demonstrated that the area under curve and the peak concentration of optimized cubosomes were 3.1-fold and 3.3-fold, respectively, which was significantly higher than marketed eye drops. Moreover, histopathological studies illustrated the existence of normal ocular structures, thus indicating that there was no damage to the corneal epithelium or stromal layer. Consequently, the results acquired demonstrated that tobramycin-loaded cubosomal formulation could be a propitious lipid-based nanodelivery system that would enhance retention time and corneal permeability contrast to commercial eye drops.

26 Nov 2020·Recent patents on anti-infective drug discovery

Investigating The Retention Potential of Chitosan Nanoparticulate Gel: Design, Development, In Vitro & Ex Vivo Characterization

Article

Author: Kaul, Shreya ; Pandey, Jaya ; Nagaich, Upendra ; Jain, Neha

Introduction::

The main purpose of the research was to develop, optimize and characterize tobramycin sulphate loaded chitosan nanoparticles based gel in order to ameliorate its therapeutic efficacy, precorneal residence time, stability, targeting and to provide controlled release of the drug.

Methods::

Box-Behnken design was used to optimize formulation by 3-factors (chitosan, STPP and tween 80) and 3-levels. Developed formulation was subjected for characterizations such as shape and surface morphology, zeta potential, particle size, in vitro drug release studies, entrapment efficiency of drug, visual inspection, pH, viscosity, spreadability, drug content, ex vivo transcorneal permeation studies, ocular tolerance test, antimicrobial studies, isotonicity evaluation and histopathology studies.

Results::

Based on the evaluation parameters, the optimized formulation showed a particle size of 43.85 ± 0.86 nm and entrapment efficiency 91.56% ± 1.04, PDI 0.254. Cumulative in vitro drug release was up to 92.21% ± 1.71 for 12 hours and drug content was found between 95.36% ± 1.25 to 98.8% ± 1.34. TEM analysis unfolded spherical shape of nanoparticles. TS loaded nanoparticulate gel exhibited significantly higher transcorneal permeation as well as bioadhesion when compared with marketed formulation. Ocular tolerance was evaluated by HET-CAM test and formulation was non-irritant and well-tolerated. Histopathology studies revealed that there was no evidence of damage to the normal structure of the goat cornea. As per ICH guidelines, stability studies were conducted and were subjected for 6 months.

Conclusion::

Results revealed that the developed formulation could be an ideal substitute for conventional eye drops for the treatment of bacterial keratitis.

01 Mar 2020·Environmental science and pollution research internationalQ3 · ENVIRONMENTAL SCIENCE & ECOLOGY

Ecotoxicological study of six drugs in Aliivibrio fischeri, Daphnia magna and Raphidocelis subcapitata

Q3 · ENVIRONMENTAL SCIENCE & ECOLOGY

Article

Author: Cannavò, Mariachiara ; Aso, Elena ; Ros, Natalia ; Lapeña, David ; Errazquin, Diego ; Giner, Beatriz ; Lomba, Laura

The presence of drugs in the environment is an emerging issue in the scientific community. It has been shown that these substances are active chemicals that consequently affect aquatic organisms and, finally, humans as end users. To evaluate the toxicity of these compounds and how they affect the environment, it is important to perform systematic ecotoxicological and physicochemical studies. The best way to address this problem is to conduct studies on different aquatic trophic levels. In this work, an ecotoxicological study of six drugs (anhydrous caffeine, diphenhydramine hydrochloride, gentamicin sulphate, lidocaine hydrochloride, tobramycin sulphate and enalapril maleate) that used three aquatic biological models (Raphidocelis subcapitata, Aliivibrio fischeri and Daphnia magna) was performed. Additionally, the concentration of chlorophyll in the algae R. subcapitata was measured. Furthermore, EC50 values were analysed using the Passino and Smith classification (PSC) method, which categorized the compounds as toxic or relatively toxic. All of the studied drugs showed clear concentration-dependent toxic effects. The toxicity of the chemicals depended on the biological model studied, with Raphidocelis subcapitata being the most sensitive species and Aliivibrio fischeri being the least sensitive. The results indicate that the most toxic compound, for all the studied biological models, was diphenhydramine hydrochloride. Graphical abstract.

News (Medical) associated with Tobramycin Sulfate

06 Jun 2024

·www.globenewswire.com

Osteal Therapeutics Closes $50M Series D Financing to Support Approval and Commercial Launch of Lead Candidate

Financing led by Zimmer Biomet with participation from existing investors Johnson & Johnson Innovation – JJDC, Inc., Gideon Strategic Partners, and HM Capital. Proceeds will support NDA submission and commercial launch of lead candidate, VT-X7, a 7-day treatment for periprosthetic joint infection. June 05, 2024 -- Osteal Therapeutics, Inc. (“Osteal”), a clinical-stage biopharmaceutical company developing a new category of combination drug/device therapies for orthopedic infections, announced today the completion of an oversubscribed $50 million Series D preferred stock equity financing. Zimmer Biomet led the round, joined by returning investors Johnson & Johnson Innovation – JJDC, Inc., Gideon Strategic Partners, and HM Capital. In conjunction with the financing, a representative of Zimmer Biomet will join Osteal’s Board of Directors. The proceeds of the financing will be used to advance the development of Osteal’s portfolio of therapies, including the submission of a New Drug Application (NDA) for, and accelerated commercial launch of, VT-X7 for the treatment of periprosthetic joint infection (PJI) of the hip and knee. VT-X7 has been the subject of two multicenter, randomized, controlled trials, APEX and APEX-2. APEX-2 recently met its primary endpoint and will be completed in late 2024. The study builds upon the safety and efficacy evidence obtained from APEX, a similarly designed clinical study that successfully met its primary endpoint in 2023. Both studies were designed in close consultation with the FDA, which previously granted VT-X7 Breakthrough Therapy, Orphan Drug, Fast Track, and Qualified Infectious Disease Product designations. The company expects to seek FDA approval upon completion of APEX-2. “This round of financing represents an inflection point in the company’s progress towards introducing VT-X7 to the market,” said David Thompson, Chairman and Chief Executive Officer. “From the beginning, Osteal has been extremely fortunate to have the support of a world-class group of financial and strategic partners who share our vision and recognize the tremendous impact our programs will have on patient care. I am delighted to welcome Zimmer Biomet as a partner and look forward to working closely with their exemplary team.” Affecting over 40,000 people in the U.S. annually, PJI is a rare and potentially devastating complication of joint replacement surgery in which pathogenic bacteria colonize the joint prosthesis, forming difficult-to-remove structures called biofilms. Biofilm infections are challenging to resolve, requiring long, invasive and expensive treatments that are often unsuccessful, resulting in high rates of permanent disability and early death. Recent retrospective analyses demonstrate that the current gold standard for treatment of PJI, two-stage exchange arthroplasty, takes an average of 16 weeks and has a success rate under 50% after 12 months, highlighting the unmet need for faster and more efficacious treatment options. VT-X7 (vancomycin hydrochloride and tobramycin sulfate for irrigation/VT-X7 irrigation system) is a novel drug/device combination product designed to deliver therapeutic concentrations of vancomycin and tobramycin, well-established, broad-spectrum antibiotics, directly to the joint space and surrounding tissue to treat PJI. VT-X7 is a seven-day therapy designed to address the unmet clinical need for a rapid, reliable treatment for these challenging infections. In clinical studies of VT-X7, 100% of patients were treated and received a new permanent joint prosthesis in seven days with >90% remaining infection-free after one year. The US Food and Drug Administration has granted VT-X7 Breakthrough Therapy, Orphan Drug, Fast Track and Qualified Infectious Disease Product designations. This initial application of VT-X7 represents a first-of-its-kind, multibillion-dollar opportunity to dramatically improve outcomes for a serious unmet medical need. Osteal Therapeutics is a privately held, clinical-stage biopharmaceutical company developing novel musculoskeletal therapeutics to treat orthopedic infections and their consequences. The company is leveraging the ability of concentrated, locally delivered antimicrobials to treat the bacterial biofilms typically responsible for musculoskeletal infections while minimizing off-target tissue exposure and associated adverse effects. Osteal employs a low-risk development strategy by using approved drugs with long histories of safety and efficacy as candidates for new routes of local delivery. The company’s lead candidate, VT-X7, is in late-stage clinical development to treat periprosthetic joint infections, a serious complication of joint replacement surgery. For more information, please visit: www.ostealtx.com The content above comes from the network. if any infringement, please contact us to modify.

Fast TrackOrphan DrugQualified Infectious Disease Product

06 Jun 2024

·www.pharmaceutical-technology.com

Osteal raises $50m to bring joint infection drug/device combo to market

Osteal antibiotic joint spacer aims to treat periprosthetic joint infection. Image credit: Shutterstock / Kateryna Kon. Osteal Therapeutics has raised $50m in Series D financing, as the orthopaedic infection treatment specialist turns its eyes to a regulatory submission for its lead candidate VT-X7. Recommended Buyer's Guides Buyer's Guide Leading Guide to Packaging Materials, Containers and Containment Services for the Pharmaceutical Industry Buyer's Guide Leading Guide to Clinical Packaging Companies in contract Manufacturing for the Pharmaceutical Industry Medtech giant Zimmer Biomet led the round with participation from existing investors, including Johnson & Johnson Innovation, among others. The funds, which follow $23m raised in Series C financing in late 2023, will be used for a new drug application (NDA) to the US Food and Drug Administration (FDA) for VT-X7. Proceeds will also go towards advancing the US-based company’s musculoskeletal portfolio , according to a 5 June press release. Osteal has designed VT-X7 for the treatment of periprosthetic joint infection. The condition is a complication of joint replacement surgery in which bacteria infiltrate the joint implant. This causes biofilms, a layer of microorganisms that are hard to treat. VT-X7 is a drug/device combination product, consisting of antibiotic drugs vancomycin hydrochloride and tobramycin sulfate for irrigation and the VT-X7 irrigation system. The therapy works by placing a spacer connected to an irrigation pump. Antibiotics are then administered into the joint space through the spacer for seven days of treatment. See Also: FDA recommends updated Covid-19 vaccines targeting JN.1 India’s DCGI approves Orchid Pharma’s API Enmetazobactam Osteal says the product can deliver high antibiotic concentrations at the infection site and is effective against both gram-negative and gram-positive bacteria. The company’s candidate has breakthrough therapy, orphan drug, fast track, and qualified infectious disease product designations, indicating that the company is eligible for a range of benefits on expedited regulatory pathways. VT-X7 recently demonstrated positive results in a Phase III trial, named APEX-2 (NCT05607030). The trial, which enrolled 76 patients scheduled for a two-stage exchange arthroplasty due to hip or knee periprosthetic joint infection, met its primary endpoint of treatment success after 180 days. The trial is expected to end in late 2024, at which point Osteal said it will seek FDA approval. Osteal’s CEO David Thompson said: “This round of financing represents an inflection point in the company’s progress towards introducing VT-X7 to the market.”

Clinical ResultPhase 3Fast TrackOrphan DrugVaccine

05 Dec 2023

·www.globenewswire.com

Osteal Therapeutics’ VT-X7 Receives FDA’s Breakthrough Therapy Designation for the treatment of periprosthetic joint infection of the hip and knee and completes enrollment of the pivotal APEX-2 trial

Breakthrough Therapy Designation for VT-X7 builds upon previous Orphan Drug, Qualified Infectious Disease Product (QIDP) and Fast Track DesignationsDALLAS, Dec. 05, 2023 (GLOBE NEWSWIRE) -- The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for VT-X7, Osteal Therapeutics’ (“Osteal’s”) investigational drug therapy for periprosthetic joint infection (“PJI”) of the hip and knee. Breakthrough Therapy Designation helps to accelerate commercialization of new drugs for the treatment of serious conditions when early clinical evidence shows the potential to provide a significant improvement of current standard of care. Previously, FDA granted VT-X7 Orphan Drug, Qualified Infectious Disease Product and Fast Track designations. The company also announced completion of enrollment in APEX-2 the pivotal clinical trial for VT-X7. “Receiving Breakthrough Therapy Designation from FDA is a significant achievement for the company and reflects FDA’s recognition of VT-X7’s potential in the treatment of PJI as a serious, life-threatening condition,” said David Thompson, President and Chief Executive Officer. “Patients and providers desperately need a better option for treating PJI. This designation supports the potential for VT-X7 to transform PJI treatment and puts us on an accelerated pathway to addressing this need.” “We are pleased to see VT-X7 receive Breakthrough Therapy Designation from FDA. In this market where there are no FDA approved products for treatment of PJI, Osteal offers one of the most compelling advances in PJI treatment we have ever seen,” said Judson Cooper of Prism Ventures. “By virtually eliminating the interstage period associated with traditional two-stage exchange arthroplasty, VT-X7 could put patients on the path to normal life sooner without the morbidity and mortality associated with this lengthy period of limited mobility.” Breakthrough Therapy designation was granted based on results from APEX (NCT04662632), a Phase 2b, prospective, multi-center, randomized controlled clinical trial evaluating the safety and efficacy of VT-X7. FDA’s Breakthrough Therapy program is designed to expedite development review of drugs intended to treat a serious or life-threatening condition for which preliminary clinical evidence indicates the drug may demonstrate substantial improvement over available therapies. About Periprosthetic Joint Infection (PJI) Affecting over 40,000 people in the U.S annually, PJI is a rare and potentially devastating complication of joint replacement surgery in which pathogenic bacteria colonize the joint prosthesis forming difficult to remove structures called biofilms. Biofilm infections are challenging to resolve, requiring long, invasive and expensive treatments that are often unsuccessful, resulting in high rates of permanent disability and early death. Recent retrospective analyses demonstrate that the current gold standard for treatment of PJI, two-stage exchange arthroplasty, takes an average of 16 weeks and has a success rate under 50% after 12 months, highlighting the unmet need for faster and more efficacious treatment options. About VT-X7 VT-X7 (vancomycin hydrochloride and tobramycin sulfate for irrigation/VT-X7 irrigation system) is a novel drug/device combination product designed to deliver therapeutic concentrations of vancomycin and tobramycin, well-established, broad-spectrum antibiotics, directly to the joint space and surrounding tissue to treat PJI. VT-X7 is a seven-day therapy designed to address the unmet clinical need for a rapid, reliable treatment for these challenging infections. In a Phase 2 clinical study of VT-X7, 100% of patients were treated and received a new permanent joint prosthesis in seven days with 93% remaining infection free at one year. The US FDA granted VT-X7 Breakthrough Therapy, orphan drug, fast track, priority review and qualified infectious disease product designations. This initial application of VT-X7 represents a first-of-its-kind, multibillion dollar opportunity to dramatically improve outcomes for a serious unmet medical need. About Osteal Therapeutics, Inc. Osteal Therapeutics is a privately held, clinical-stage biopharmaceutical company developing novel musculoskeletal therapeutics to treat orthopedic infections and their consequences. The company is leveraging the ability of concentrated, locally delivered antimicrobials to treat the bacterial biofilms typically responsible for musculoskeletal infections while minimizing off-target tissue exposure and associated adverse effects. Osteal employs a low-risk development strategy by using approved drugs with long histories of safety and efficacy as candidates for new routes of local delivery. The company’s lead candidate, VT-X7, is in late-stage clinical development to treat periprosthetic joint infections, a serious complication of joint replacement surgery. For more information, please visit: www.ostealtx.com Media Contacts: Osteal Therapeutics, Inc.Todd SaundersVice President of MarketingEmail: info@ostealtx.com

Fast TrackOrphan DrugPhase 2Qualified Infectious Disease ProductBreakthrough Therapy

100 Deals associated with Tobramycin Sulfate

External Link

KEGG	Wiki	ATC	Drug Bank
D02542	Tobramycin Sulfate	S01AA12 J01GB01	DB00684

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Cystic Fibrosis	EU	PARI Pharma GmbH	18 Feb 2019
Cystic Fibrosis	IS	PARI Pharma GmbH	18 Feb 2019
Cystic Fibrosis	LI	PARI Pharma GmbH	18 Feb 2019
Cystic Fibrosis	NO	PARI Pharma GmbH	18 Feb 2019
Infectious Lung Disorder	EU	PARI Pharma GmbH	18 Mar 2015
Infectious Lung Disorder	IS	PARI Pharma GmbH	18 Mar 2015
Infectious Lung Disorder	LI	PARI Pharma GmbH	18 Mar 2015
Infectious Lung Disorder	NO	PARI Pharma GmbH	18 Mar 2015
Pseudomonas Infections	EU	PARI Pharma GmbH	18 Mar 2015
Pseudomonas Infections	IS	PARI Pharma GmbH	18 Mar 2015
Pseudomonas Infections	LI	PARI Pharma GmbH	18 Mar 2015
Pseudomonas Infections	NO	PARI Pharma GmbH	18 Mar 2015
Lower Respiratory Tract Infections	US	Fresenius Kabi USA LLC	13 Jul 2004
Meningitis	US	Fresenius Kabi USA LLC	13 Jul 2004
Peritonitis	US	Fresenius Kabi USA LLC	13 Jul 2004
Sepsis	US	Fresenius Kabi USA LLC	13 Jul 2004
Skin and skin structure infections	US	Fresenius Kabi USA LLC	13 Jul 2004
Urinary Tract Infections	US	Fresenius Kabi USA LLC	13 Jul 2004
Bacterial Infections	US	Eli Lilly & Co.	11 Jun 1975

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Juvenile Polyposis Syndrome	Phase 2	US	Osteal Therapeutics, Inc.	01 Nov 2021
Prosthetic joint infection	Phase 2	US	Osteal Therapeutics, Inc.	01 Nov 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03721328 (CTgov)	Phase 2	Prosthetic joint infection \| Juvenile Polyposis Syndrome	15	tobramycin sulfate+vancomycin hydrochloride	pmrckwvhms(hfcjmkbawy) = fyvhwlemwg bjljhllifl (kzislxnelz, frtxcatlgd - lmudxafnhj) View more	-	09 Dec 2021
NCT00885365 (CTgov)	Phase 3	Cystic Fibrosis \| Pseudomonas aeruginosa infection	324	tobramycin / Bramitob (Bramitob)	oomgyohxkr(qosefhkbjg) = afxxhxrshl tjnftmfqvu (bkgkqbytlk, ddjouoreil - bqxddxgahg) View more	-	20 Jun 2014
NCT00885365 (CTgov)	Phase 3	Cystic Fibrosis \| Pseudomonas aeruginosa infection	324	tobramycin / TOBI (TOBI)	oomgyohxkr(qosefhkbjg) = jlxgpmvuxc tjnftmfqvu (bkgkqbytlk, wazvofitae - aqudvalaza) View more	-	20 Jun 2014

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