Dataset Information

Favorable Pharmacokinetic Characteristics of Extended-Half-Life Recombinant Factor VIII BAY 94-9027 Enable Robust Individual Profiling Using a Population Pharmacokinetic Approach.

ABSTRACT:

Background

Prophylaxis with factor VIII (FVIII) should be individualized based on patient characteristics, including FVIII pharmacokinetics. Population pharmacokinetic (popPK) modeling simplifies pharmacokinetic studies by obviating the need for multiple samples.

Objective

The objective of this study was to characterize the pharmacokinetics and inter-individual variability (IIV) of BAY 94-9027 in relation to patient characteristics in support of a popPK-tailored approach, including identifying the optimal number and timing of pharmacokinetic samples.

Methods

Pharmacokinetic samples from 198 males (aged 2?62 years) with severe hemophilia A, enrolled in BAY 94-9027 clinical trials, were analyzed. Baseline age, height, weight, body mass index, lean body weight (LBW), von Willebrand factor (VWF) level, and race were evaluated. A popPK model was developed and used to simulate pharmacokinetic endpoints difficult to observe from measured FVIII levels, including time to maintain FVIII levels above 1, 3, and 5 IU/dL after different BAY 94-9027 doses.

Results

A one-compartment model adequately described BAY 94-9027 pharmacokinetics. Clearance and central volume of distribution were significantly associated with LBW; clearance was inversely correlated with VWF. Due to the monophasic pharmacokinetics and well-understood IIV sources, identification of patient pharmacokinetics was achievable with sparse blood sampling. Median predicted time to maintain FVIII levels >?1 IU/dL in patients aged ??12 years ranged from 120.1 to 127.2 h after single BAY 94-9027 doses of 45?60 IU/kg.

Conclusions

This analysis evaluated the pharmacokinetics of BAY 94-9027 and its sources of IIV. Using the model, determination of individual patient pharmacokinetics was possible with few FVIII samples, and a sparse sampling design to support pharmacokinetic-guided dosing was identified.

SUBMITTER: Solms A

PROVIDER: S-EPMC7217814 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Favorable Pharmacokinetic Characteristics of Extended-Half-Life Recombinant Factor VIII BAY 94-9027 Enable Robust Individual Profiling Using a Population Pharmacokinetic Approach.

Solms Alexander A Iorio Alfonso A Ahsman Maurice J MJ Vis Peter P Shah Anita A Berntorp Erik E Garmann Dirk D

Clinical pharmacokinetics 20200501 5

<h4>Background</h4>Prophylaxis with factor VIII (FVIII) should be individualized based on patient characteristics, including FVIII pharmacokinetics. Population pharmacokinetic (popPK) modeling simplifies pharmacokinetic studies by obviating the need for multiple samples.<h4>Objective</h4>The objective of this study was to characterize the pharmacokinetics and inter-individual variability (IIV) of BAY 94-9027 in relation to patient characteristics in support of a popPK-tailored approach, includin ...[more]

PMID: 31749076

Similar Datasets

Project description:IntroductionBAY 94-9027 is a newly developed extended half-life product to treat haemophilia, allowing for fewer injections than with standard products. This post hoc analysis aimed to compare physicians' and patients' opinions on BAY 94-9027 prophylaxis, and explore how qualitative interview data is aligned with the data from the Haemophilia-specific Quality of Life questionnaire for Adults (Haemo-QoL-A).MethodsExploratory qualitative interviews were conducted with physicians and patients by phone upon the exit of patients from the PROTECT VIII extension phase following a semi-directed guide. In this post hoc analysis, all transcripts were reviewed and reported concepts were compared to assess the level of concordance between physicians and patients. These qualitative data were compared with the Haemo-QoL-A mean global and subscale scores at baseline and end of main phase (36 weeks later).ResultsTen physicians and 16 patients (mean age 47 years) from Israel, the Netherlands and the USA were interviewed. Significant improvements were reported by all physicians from baseline [e.g. lower frequency of bleeds (80%), improvement in emotional functioning (90%)], which is in concordance with patients' reports. The improved confidence reported by physicians cascaded to greater participation in various activities, resulting in a better perceived emotional state and a significant improvement on the Haemo-QoL-A emotional impact subscale score (p = 0.04) between baseline and end of main phase. Most physicians (80%) reported improvement in bleed frequency, as patients did (88%). Improvement in physical functioning or mobility was not consistently reported in this 8-month study.ConclusionInterviewed physicians and patients generally agreed on the beneficial impact of BAY 94-9027, specifically regarding the increased level of self-confidence in patients and its subsequent positive impact on patients' lives. These findings supported the observed improvement on the Haemo-QoL-A emotional impact subscale. Overall, this study highlights the concordance between physician and patient perspective on the positive experience with BAY 94-9027.

Dataset Information

Favorable Pharmacokinetic Characteristics of Extended-Half-Life Recombinant Factor VIII BAY 94-9027 Enable Robust Individual Profiling Using a Population Pharmacokinetic Approach.

Background

Objective

Methods

Results

Conclusions

Publications

Favorable Pharmacokinetic Characteristics of Extended-Half-Life Recombinant Factor VIII BAY 94-9027 Enable Robust Individual Profiling Using a Population Pharmacokinetic Approach.

Similar Datasets

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