Sailstad J.M.,NC Associates |
Amaravadi L.,Biogen Idec |
Clements-Egan A.,Janssen Research and Development Johnson and Johnson |
Gorovits B.,Pfizer |
And 8 more authors.
AAPS Journal | Year: 2014
The Global Bioanalysis Consortium (GBC) set up an international team to explore the impact of immunogenicity on pharmacokinetic (PK) assessments. The intent of this paper is to define the field and propose best practices when developing PK assays for biotherapeutics. We focus on the impact of anti-drug antibodies (ADA) on the performance of PK assay leading to the impact on the reported drug concentration and exposure. The manuscript describes strategies to assess whether the observed change in the drug concentration is due to the ADA impact on drug clearance rates or is a consequence of ADA interference in the bioanalytical method applied to measure drug concentration. This paper provides the bioanalytical scientist guidance for developing ADA-tolerant PK methods. It is essential that the data generated in the PK, ADA, pharmacodynamic and efficacy/toxicity evaluations are viewed together. Therefore, the extent for the investigation of the PK sensitivity to the presence of ADA should be driven by the project needs and risk based. © 2014 American Association of Pharmaceutical Scientists.
Van Boxtel R.A.J.,National Institute for Public Health and the Environment RIVM |
Verdijk P.,Institute for Translational Vaccinology Intravacc |
de Boer O.J.,Institute for Translational Vaccinology Intravacc |
van Riet E.,Institute for Translational Vaccinology Intravacc |
And 2 more authors.
Human Vaccines and Immunotherapeutics | Year: 2015
Background: Influenza vaccine production capacity is still insufficient to meet global demand in case of a pandemic. To expand worldwide influenza vaccine production capacity, a solid and transferable egg-based influenza vaccine production process was established that is suitable for upscaling and technology transfer to vaccine manufacturers in low- and middle-income countries. As a proof-of-concept, the safety and immunogenicity of a pandemic whole inactivated virus (WIV) vaccine (H5N1) and a monovalent seasonal WIV vaccine (H3N2) were evaluated in a phase I clinical trial in adults. METHODS: Subjects were vaccinated with 2 doses of pandemic WIV vaccine (pWIV), or one dose of either seasonal WIV vaccine (sWIV) or a commercially available trivalent comparator vaccine followed by a placebo dose. Haemagglutination inhibiting antibody titres against the influenza strains were determined before and 21 d after each vaccination. RESULTS: The frequency and severity of adverse reactions were comparable between groups. No serious adverse events were reported. After a single dose of sWIV the seroconversion rate was 91% (Committee for Proprietary Medicinal Products (CPMP) criterion >40%), the seroprotection rate was 100% (CPMP criterion >70%), and the mean geometric mean titre (GMT) increase was 24.9 (CPMP criterion >2.5). After two doses of pWIV, seroconversion rate and seroprotection rate were both 71%, and the mean GMT increase was 7.8. CONCLUSIONS: Both pWIV and sWIV were equally well-tolerated as the comparator vaccine, and both vaccines complied with all 3 CPMP criteria. EudraCT 2011-000159-17. Netherlands National Trial Register 2695. © 2015 Taylor & Francis Group, LLC.
Gerrits M.G.F.,MSD Netherlands |
Gerrits M.G.F.,Merck And Co. |
Kramer H.,MSD Netherlands |
Galta R.E.,MSD Netherlands |
And 6 more authors.
Fertility and Sterility | Year: 2016
Objective To assess the safety, pharmacokinetics, and pharmacodynamics of MK-8389. Design Double-blind, placebo-controlled, parallel-group, ascending dose study. Setting Two clinical research organizations. Patient(s) Healthy young women. Intervention(s) Once-daily oral doses of MK-8389 or placebo for 14 days. Main Outcome Measure(s) Safety, including thyroid function tests (TFTs), pharmacokinetics, and follicular development (follicle size and number and serum E2 and inhibin B levels). Result(s) Treatment with MK-8389 was generally safe and well tolerated. An effect on TFTs was observed, which was transient and did not lead to clinical signs or symptoms but prevented dose escalation above 40 mg. MK-8389 was rapidly absorbed, slowly eliminated, and showed a large peak-to-trough ratio. No clinically meaningful effect was seen on follicle size and numbers, which was consistent with the low E2 levels. At doses >20 mg, inhibin B levels were increased, suggesting early follicular development at higher doses. Conclusion(s) Oral administration of MK-8389 demonstrated acceptable systemic exposure and was generally well tolerated. This study failed to demonstrate a clinically meaningful effect of MK-8389 on follicular development, whereas MK-8389 unexpectedly affected thyroid function. This study did not explore doses above 40 mg given the changes observed in TFTs, which may relate to high MK-8389 peak concentrations. Clinical Trial Registration Number EudraCT Number 2010-022396-57. © 2016 American Society for Reproductive Medicine.
de Boer T.,QPS Netherlands |
Wieling J.,QPS Netherlands |
Meulman E.,QPS Netherlands |
Reuvers M.,QPS Netherlands |
And 5 more authors.
Biomedical Chromatography | Year: 2011
An early clinical development study (phase I) was conducted to determine the usefulness of dried blood spot (DBS) sampling as an alternative to venous sampling for phenotyping and genotyping of CYP450 enzymes in healthy volunteers. Midazolam (MDZ) was used as a substrate for phenotyping CYP3A4 activity; the concentrations of MDZ and its main metabolite 1'-hydroxymidazolam (1-OH MDZ) were compared between the DBS method from finger punctures, plasma and whole blood (WB), drawn by venipuncture, whereby several methodological parameters were studied (i.e. punch width, amount of dots analyzed and storage time stability). Genotyping between DBS and venous WB samples was compared for CYP2D6 (*3, *4, *6), CYP2C19 (*2, *3), CYP3A4 (*1B) and CYP3A5 (*3C). In addition, the subject's and phlebotomist's satisfaction with venous blood sampling compared with the DBS method was evaluated using a standardized questionnaire. An LC-MS/MS method for the quantification of the MDZ and 1-OH MDZ concentrations in DBS samples was developed and validated in the range of 0.100-100ng/mL. No compromises were made for the limits of quantification of the DBS-LC-MS/MS method vs the authentic plasma and WB methods. © 2011 John Wiley & Sons, Ltd.
Lowes S.,Advion BioServices Inc. |
Jersey J.,Agilux Laboratories |
Shoup R.,AIT Bioscience |
Garofolo F.,Algorithme Pharma Inc. |
And 40 more authors.
Bioanalysis | Year: 2011
The Global CRO Council (GCC) for Bioanalysis was formed in an effort to bring together many CRO leaders to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. © 2011 Future Science Ltd.