Population pharmacokinetic/pharmacodynamic modeling of tumor growth kinetics in medullary thyroid cancer patients receiving cabozantinib.

Nonlinear mixed effects models were developed to describe the relationship between cabozantinib exposure and target lesion tumor size in a phase III study of patients with progressive metastatic medullary thyroid cancer. These models used cabozantinib exposure estimates from a previously published population pharmacokinetic model for cabozantinib in cancer patients that was updated with data from […]

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Modeling and Simulation to Support Phase 2 Dose Selection for RG7652, a Fully Human Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9.

RG7652 is a fully humanized monoclonal antibody targeting human PCSK9, a regulator of serum low density lipoprotein cholesterol (LDLc) levels. RG7652 prevents degradation of the hepatic LDLc receptors by blocking PCSK9 binding and thereby resulting in efficient LDLc uptake by hepatocytes. The pharmacokinetics of RG7652 have been evaluated in healthy subjects after single and multiple […]

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Model-based meta-analysis for quantifying Paclitaxel dose response in cancer patients

Model-based meta-analysis of dose response is a sophisticated method to guide dose and regimen selection. In this report, the effects of paclitaxel dose and regimen (weekly or every 3 weeks) on the efficacy and safety in cancer patients were quantified by model-based meta-analysis of 29 monotherapy trials. Logistic regression models were developed to assess the […]

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Placebo response changes depending on the neuropathic pain syndrome: results of a systematic review and meta-analysis

The purpose of this study was to compare placebo responses in neuropathic pain syndromes through systematic literature review and meta-analysis. We used randomized placebo-controlled trials assessing pain intensity or pain relief in any neuropathic pain syndrome published since 1995 with +AD4-/+AD0-5days follow-up. We measured placebo response as measured by pain intensity and responder rates (proportion reporting +AD4-/+AD0-50+ACU- pain […]

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Model-based meta-analysis for comparative efficacy and safety: application in drug development and beyond

High development cost, low development success, cost-disciplined health-care policies, and intense competition demand an efficient drug development process. New compounds need to bring value to patients by being safe, efficacious, and cost-effective as compared with existing treatment options. Model-based meta-analysis (MBMA) facilitates integration and utilization of summary-level efficacy and safety data, providing a quantitative framework […]

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Population pharmacokinetics of olmesartan following oral administration of its prodrug, olmesartan medoxomil: in healthy volunteers and hypertensive patients

Olmesartan medoxomil (CS-866) is a new orally active angiotensin II receptor antagonist that is highly selective for the AT1 receptor subtype. The objective of this study was to develop a population pharmacokinetic model for olmesartan (RNH-6270), the active metabolite of olmesartan medoxomil, in healthy volunteers and hypertensive patients, and to evaluate effects of covariates on […]

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Predictive population pharmacokinetic/pharmacodynamic model for a novel COX-2 inhibitor

The objectives of these analyses were to (1) develop a population pharmacokinetic/pharmacodynamic model for a novel COX-2 inhibitor (CS-706) using data from primarily Caucasian subjects, (2) predict responses in subpopulations of interest (including Japanese subjects), and (3) correlate pharmacodynamic parameters to safety outcomes. The model was developed using data from 130 healthy adults following single […]

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Development of a predictive pharmacokinetic model for a novel cyclooxygenase-2 inhibitor

A predictive population pharmacokinetic model was developed for a novel cyclooxygenase-2 (COX-2) inhibitor CS-706, using data from 130 subjects in 3 phase 1 trials after single or multiple doses of CS-706 (2- to 800-mg doses daily, up to 14 days) and validated using sparse data from a separate study. A 2-compartment model described the data. […]

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Combining drug-disease and economic modelling to inform drug development decisions

Drug-disease models and clinical trial simulations are increasingly being used to support trial design and treatment optimization decisions.  Less widely recognized is their potential for guiding strategic development decisions.  These decisions require economic valuation of the potential product profile of efficacy, safety, ease of use, and so on.  This review presents a disguised case study […]

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Pain relief model for a COX-2 inhibitor in patients with postoperative dental pain

AIM: To develop a pain relief model for a cyclooxygenase (COX)-2 inhibitor, CS-706, that permits prediction of doses for acute pain relief in Japanese and Western populations. METHODS: A categorical response model was developed to describe the probability of pain relief (PR) over time for a Phase 2a study. Models were also developed to describe […]

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