Pharmacokinetics and Tolerability of Obiltoxaximab: A Report of 5 Healthy Volunteer Studies

Nagy, Christa F.; Leach, Timothy; Hoffman, Joseph H.; Czech, Arthur; Carpenter, Sarah; Guttendorf, Robert

doi:10.1016/j.clinthera.2016.07.170

Cited by 16 publications

(38 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the conduct of the study the protocol was amended to include pretreatment with 50 mg of oral diphenhydramine 30 minutes prior to study drug administration. This was based on preliminary results from clinical trials in healthy subjects administered obiltoxaximab intravenously, in which some subjects experienced hypersensitivity reactions during or shortly after the infusion of obiltoxaximab …”

Section: Methodsmentioning

confidence: 99%

“…Serum samples were assayed for free obiltoxaximab concentrations using a validated enzyme‐linked immunosorbent assay method in which PA83 is used as the capture reagent . Selectivity was demonstrated in individual lots of normal human serum in the presence of spiked obiltoxaximab at 300 and 3000 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

“…As intramuscular and intravenous obiltoxaximab data were not available within the same clinical study, intramuscular obiltoxaximab bioavailability in humans was estimated based on a cross‐study evaluation using ratios of mean systemic CL following a 16 mg/kg intravenous dose of obiltoxaximab to mean CL/F values for each dose group after intramuscular administration of obiltoxaximab in the current study based on the formula:

\begin{matrix} true \\ right F & = & left ((), AU C_{IM} / Dos e_{IM}) / ((), AU C_{IV} / Dos e_{IV}) \\ = & left ([], 1 / ((), CL / F_{IM})) / ((), 1 / normalC L_{IV}) \\ = & left normalC L_{IV} / ((), CL / F_{IM}) . \end{matrix}

…”

Section: Methodsmentioning

confidence: 99%

“…ATA detection followed a tiered approach (screening and confirmatory assays) using a validated electrochemiluminescence method . Serum samples were first subjected to a minimum required dilution of 1:10.…”

Section: Methodsmentioning

confidence: 99%

“…Obiltoxaximab was developed under the US Food and Drug Administration's Animal Rule regulation (21 CFR 601.90), which is specifically intended for agents for which the conduct of definitive human efficacy studies is not ethical or feasible, as in the case of agents for the treatment of anthrax . The obiltoxaximab intravenous dose of 16 mg/kg was selected and justified based on efficacy data in animals and pharmacokinetic (PK) data in animals and healthy human volunteers, as well as population modeling of PK and efficacy data …”

mentioning

confidence: 99%

See 4 more Smart Citations

Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans

Nagy

Leach²,

King

et al. 2017

Clinical Pharm in Drug Dev

Self Cite

View full text Add to dashboard Cite

Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high-affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6-9 days, and terminal half-life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection-site abscesses or hypersensitivity reactions occurred; no subjects developed treatment-emergent antitherapeutic antibodies over the study period of 71 days.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

\begin{matrix} true \\ right F & = & left ((), AU C_{IM} / Dos e_{IM}) / ((), AU C_{IV} / Dos e_{IV}) \\ = & left ([], 1 / ((), CL / F_{IM})) / ((), 1 / normalC L_{IV}) \\ = & left normalC L_{IV} / ((), CL / F_{IM}) . \end{matrix}

…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans

Nagy

Leach²,

King

et al. 2017

Clinical Pharm in Drug Dev

Self Cite

View full text Add to dashboard Cite

show abstract

Antibody–Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections

Darbandi,

Abdi,

Dashtbin

et al. 2024

Clinical Laboratory Analysis

View full text Add to dashboard Cite

IntroductionAntibodies are significant agents in the immune system and have proven to be effective in treating bacterial infections. With the advancement of antibody engineering in recent decades, antibody therapy has evolved widely.AimThis review aimed to investigate a new method as a therapeutic platform for the treatment of bacterial infections and explore the novel features of this method in conferring pathogen specificity to broad‐spectrum antibiotics.Material and MethodsA literature review was conducted addressing the following topics about antibody–antibiotic conjugates (AACs): (1) structure and mechanism of action; (2) clinical effectiveness; (3) advantages and disadvantages.ResultAntibody conjugates are designed to build upon the progress made in the development of monoclonal antibodies for the treatment of diseases. Despite the growing emergence of antibiotic resistance among pathogenic bacteria worldwide, novel antimicrobials have not been sufficiently expanded to combat the global crisis of antibiotic resistance. A recently developed strategy for the treatment of infectious diseases is the use of AACs, which are specifically activated only in host cells.ConclusionA novel therapeutic AAC employs an antibody to deliver the antibiotic to the bacteria. The AACs can release potent antibacterial components that unconjugated forms may not exhibit with an appropriate therapeutic index. This review highlights how this science has guided the design principles of an impressive AAC and discusses how the AAC model promises to enhance the antibiotic effect against bacterial infections.

show abstract

Population Pharmacokinetics (PopPK) Support for Pediatric Dosing of Biological Products

Eales,

Helal,

Vattelana

et al. 2024

The Journal of Clinical Pharma

View full text Add to dashboard Cite

This study assesses the use of population pharmacokinetics (PopPK) in supporting pediatric dosing of novel biological drug products. The labeling for biologic drug products approved by the US Food and Drug Administration (FDA) from 2002 until 2021 was reviewed to identify those with a pediatric indication. For the drugs with a pediatric indication, the dosing regimen(s) based on age groups, dosing strategy, the use of PopPK to support the dose, and the types of pediatric clinical trials were reviewed. Data were collected from FDA's review documents and product labels on the Drugs@FDA website, and as needed, more clinical trial details were collected from PubMed and clinicaltrials.gov. The role of PopPK analyses in dosing was captured when mentioned in the label or review as playing a role in selecting the approved pediatric dose and/or in verifying the adequacy of the studied dose to support labeling. Between 2002 and 2021, FDA approved 169 biological products, and 78 of 169 (46%) products have an approved indication for which the label contains dosing recommendations for pediatric use. For the 78 products approved in pediatrics, there was a total of 180 clinical trials that included pediatric patients. Phase 3 pediatric trials commonly supported pediatric approval and dosing for the reviewed products (64%, 50/78 products; 56.1%, 101/180 trials). PopPK analyses were reported to play a critical role in dose selection, prediction, and verification for 40 of the 78 products (51%), including informing pediatric dosing in the absence of pediatric data (e.g., drugs approved under animal rule), comparing exposures to the exposure range observed in adults, and informing alternative dosing strategies in certain age or body weight groups. PopPK analyses have been applied in a variety of ways to inform pediatric dosing and support extrapolation from adult data or other pediatric age groups for biologics. Understanding and learning from these past cases on the use of pharmacometrics tools to support pediatric dosing of biological products can inform future pediatric development programs.

show abstract

Pharmacokinetics and Tolerability of Obiltoxaximab: A Report of 5 Healthy Volunteer Studies

Cited by 16 publications

References 20 publications

Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans

Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans

Antibody–Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections

Population Pharmacokinetics (PopPK) Support for Pediatric Dosing of Biological Products

Contact Info

Product

Resources

About