Posted On: 09/19/2015 11:47:19 AM
Post# of 72443
Brilacidin poster. We're getting ready for peer review as well for Kevetrin and it will be easy to get peer review for Brilacidin as well. Science is continuing to outperform. Just a matter of time before the pps reacts and starts heading where it should be.
http://cellceutix.com/wp-content/uploads/2014...r-Walk.pdf
RESULTS Data Description • A total of 2,960 plasma brilacidin concentrations collected from 391 individuals were used to construct the population PK model. • The PK analysis population was 73.2% male and had a median (min, max) weight of 78.0 (42.0, 145) kg, age of 40.0 (18, 79) years, BSA of 1.91 (1.34, 2.56) m2, and CLcr of 97.3 (21.0, 190) mL/ min/1.73 m2. Population PK Analysis • A three-compartment model with zero-order input and first-order elimination best described brilacidin PK in both healthy subjects and patients with ABSSSI. • The final population PK model parameter estimates and associated standard errors are provided in Table 1 and selected GOF plots stratified by study are shown in Figure 2. o The observed brilacidin concentrations were in good agreement with both the population predicted concentrations (r2=0.75) and individual post-hoc predicted concentrations (r2=0.94) and did not exhibit any noticeable biases. Plots of the conditional weighted residuals also did not show any biases with respect to time since last dose, study, or brilacidin dose. o Residual variability was described using a constant coefficient of variation (CCV) error model and was estimated to be significantly larger in Study PMX63-203 (25.0% CV) and Study CTIX-BRI-204 (18.2% CV) relative to the well-controlled Phase 1 studies (9.58% CV)
CONCLUSIONS
METHODS ABSTRACT
• Brilacidin is a synthetic molecule that represents a novel class of antimicrobials agents that mimic the structure and function of host defense proteins. • Brilacidin acts directly on the cell membrane, disrupting its integrity and causing bacterial death and has demonstrated potent antimicrobial activity against Gram-positive and Gramnegative organisms, including methicillin-resistant Staphylococcus aureus. • Cellceutix Corporation is currently developing brilacidin for the treatment of patients with acute bacterial skin and skin structure infection (ABSSSI) caused by S. aureus. • Plasma brilacidin concentrations exhibit a poly-exponential decline, with biliary clearance (CL), the predominant route of elimination and negligible (<1%) renal elimination or hepatic metabolism. The extent of fecal excretion of radiolabeled brilacidin was shown to be 40.2% in male rats and 25.5% in female rats suggesting sex-related differences in biliary CL [1]. • The pharmacokinetics (PK) of brilacidin have previously been studied in healthy subjects in three Phase 1 studies (Studies PMX63-101, PMX63-102, and PMX63-103) and patients with ABSSSI from a Phase 2 study (StudyPMX63-203) [2]. o A linear three-compartment model with zero-order intravenous (IV) input and first-order elimination (Figure 1) was previously developed by ICPD to describe brilacidin PK.
• A three-compartment model with zero-order input and first-order elimination best described the plasma brilacidin concentration-time profile in both healthy subjects and patients with ABSSSI. • The most statistically significant parameter-covariate relationship identified was the impact of sex on brilacidin CL, for which the 21.5% faster CL in males was of marginal clinical significance, while as expected, body size was predictive of the overall Vc. • Lack of a substantial relationship between brilacidin CL and body weight in this analysis suggests that capping weight-based dosing for patients ≥90 kg, or using fixed dosing, is expected to help ensure brilacidin AUC are maintained within a safe and effective window.
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Now that is sexy.
http://cellceutix.com/wp-content/uploads/2014...r-Walk.pdf
RESULTS Data Description • A total of 2,960 plasma brilacidin concentrations collected from 391 individuals were used to construct the population PK model. • The PK analysis population was 73.2% male and had a median (min, max) weight of 78.0 (42.0, 145) kg, age of 40.0 (18, 79) years, BSA of 1.91 (1.34, 2.56) m2, and CLcr of 97.3 (21.0, 190) mL/ min/1.73 m2. Population PK Analysis • A three-compartment model with zero-order input and first-order elimination best described brilacidin PK in both healthy subjects and patients with ABSSSI. • The final population PK model parameter estimates and associated standard errors are provided in Table 1 and selected GOF plots stratified by study are shown in Figure 2. o The observed brilacidin concentrations were in good agreement with both the population predicted concentrations (r2=0.75) and individual post-hoc predicted concentrations (r2=0.94) and did not exhibit any noticeable biases. Plots of the conditional weighted residuals also did not show any biases with respect to time since last dose, study, or brilacidin dose. o Residual variability was described using a constant coefficient of variation (CCV) error model and was estimated to be significantly larger in Study PMX63-203 (25.0% CV) and Study CTIX-BRI-204 (18.2% CV) relative to the well-controlled Phase 1 studies (9.58% CV)
CONCLUSIONS
METHODS ABSTRACT
• Brilacidin is a synthetic molecule that represents a novel class of antimicrobials agents that mimic the structure and function of host defense proteins. • Brilacidin acts directly on the cell membrane, disrupting its integrity and causing bacterial death and has demonstrated potent antimicrobial activity against Gram-positive and Gramnegative organisms, including methicillin-resistant Staphylococcus aureus. • Cellceutix Corporation is currently developing brilacidin for the treatment of patients with acute bacterial skin and skin structure infection (ABSSSI) caused by S. aureus. • Plasma brilacidin concentrations exhibit a poly-exponential decline, with biliary clearance (CL), the predominant route of elimination and negligible (<1%) renal elimination or hepatic metabolism. The extent of fecal excretion of radiolabeled brilacidin was shown to be 40.2% in male rats and 25.5% in female rats suggesting sex-related differences in biliary CL [1]. • The pharmacokinetics (PK) of brilacidin have previously been studied in healthy subjects in three Phase 1 studies (Studies PMX63-101, PMX63-102, and PMX63-103) and patients with ABSSSI from a Phase 2 study (StudyPMX63-203) [2]. o A linear three-compartment model with zero-order intravenous (IV) input and first-order elimination (Figure 1) was previously developed by ICPD to describe brilacidin PK.
• A three-compartment model with zero-order input and first-order elimination best described the plasma brilacidin concentration-time profile in both healthy subjects and patients with ABSSSI. • The most statistically significant parameter-covariate relationship identified was the impact of sex on brilacidin CL, for which the 21.5% faster CL in males was of marginal clinical significance, while as expected, body size was predictive of the overall Vc. • Lack of a substantial relationship between brilacidin CL and body weight in this analysis suggests that capping weight-based dosing for patients ≥90 kg, or using fixed dosing, is expected to help ensure brilacidin AUC are maintained within a safe and effective window.
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Now that is sexy.
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