Biomarkers and Surrogate End Points for Fit-for-Purpose Development and Regulatory Evaluation of New Drugs

Ja, Wagner; Williams, S. W. D.; Webster, CJ

doi:10.1038/sj.clpt.6100017

Cited by 190 publications

(148 citation statements)

References 7 publications

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“…However, as yet few'validated'or'qualified'biomarkers are used in early-stage drug development in terms of clinical pharmacology and disease pathophysiology [12].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of LC15‐0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers

Lim¹,

Cho²,

Kim³

et al. 2009

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The importance of efficient drug development using biomarkers has been increasingly emphasized, from preclinical studies to clinical trials.• However, as yet few 'validated' or 'qualified' biomarkers are used in early-stage drug development in terms of clinical pharmacology and disease pathophysiology. WHAT THIS STUDY ADDS• This first-time-in-human study provides evidence of the pharmacological activity of LC15-0444 in humans, by using dipeptidyl peptidase IV activity and active glucagon-like peptide-1 concentrations.• LC15-0444 possesses pharmacokinetic and pharmacodynamic characteristics that support a once-daily dosing regimen. AIMSLC15-0444 is a selective and competitive inhibitor of dipeptidyl peptidase (DPP) IV with potential for the treatment of Type 2 diabetes. The aim was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles after multiple oral ascending doses of LC15-0444 in healthy male subjects. METHODSA dose block-randomized, double-blind, placebo-controlled, parallel group study was performed in three groups with 10 subjects (eight for active drug; two for placebo) per group; each group received 200, 400 or 600 mg of LC15-0444 once daily for 10 days. Blood and urine samples were collected up to 24 h after the first dosing and up to 72 h after the last dosing. RESULTSThe LC15-0444 concentration-time profiles exhibited characteristics of multicompartment disposition. No dose-or time-dependent change in PK parameters was observed. Mean elimination half-life was in a range 16.6-20.1 h in the dose groups. Mean renal clearance and fraction of unchanged drug excreted in urine was 18.6-21.9 and 0.40-0.48 l h -1 , respectively. In the steady state, mean accumulation ratios by dose groups were between 1.22 and 1.31. More than 80% inhibition of DPP IV activity from baseline was sustained for >24 h in all dose groups. CONCLUSIONSThis study provides evidence of the pharmacological activity of LC15-0444 in humans. LC15-0444 possesses PK and PD characteristics that support a once-daily dosing regimen.

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“…However, as yet few'validated'or'qualified'biomarkers are used in early-stage drug development in terms of clinical pharmacology and disease pathophysiology [12].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of LC15‐0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers

Lim¹,

Cho²,

Kim³

et al. 2009

Brit J Clinical Pharma

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“…The word biomarker itself is clearly defined 16,17 and its meaning should be consensual. However, this is the notion of potentiality associated with the word biomarker that is matter to discussion.…”

Section: Definition and Application Of Biomarkermentioning

confidence: 99%

How Shall We Use the Proteomics Toolbox for Biomarker Discovery?

2007

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Biomarker discovery for clinical purposes is one of the major areas in which proteomics is used. However, despite considerable effort, the successes have been relatively scarce. In this perspective paper, we try to figure out and analyze the main causes for this limited success, and to suggest alternate strategies, which will avoid them, without eluding the foreseeable weak points of these strategies. Two major strategies are analyzed, namely the switch from body fluids to cell and tissues for the initial biomarker discovery step or, if body fluids must be analyzed, the implementation of highly selective protein selection strategies.Keywords : proteomics ; biomarkers ; plasma ; biological fluids ; cerebrospinal fluid ; Synopsis : this paper aims at stimulating discussions on how proteomics could be best used for

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“…Recently, proteomics analysis is trying to recognize new biomarkers that can be used for diagnosis and treatment of a specific neurodegenerative disease by using the protein spectrum in the biological material such as Cerebrospinal Fluid (CSF) [32]. Biomarker as a characteristic that is objectively measured and evaluated is an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention [37]. Therefore, biomarkers are powerful tools for assessment of neurodegenerative disorders development and extent of planned therapeutics in the management of the disease [36].…”

Section: Proteomics and Neurodegenerationmentioning

confidence: 99%

Proteomics Analysis for Therapeutic Options of Neurodegeneration: A Review

Ganash¹

2017

J Proteomics Bioinform

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Biomarkers and Surrogate End Points for Fit-for-Purpose Development and Regulatory Evaluation of New Drugs

Cited by 190 publications

References 7 publications

Pharmacokinetics and pharmacodynamics of LC15‐0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers

Pharmacokinetics and pharmacodynamics of LC15‐0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers

How Shall We Use the Proteomics Toolbox for Biomarker Discovery?

Proteomics Analysis for Therapeutic Options of Neurodegeneration: A Review

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