Abstract
With the increasing cost and complexity of drug development, biomarkers will play an increasing role in the early phases. Biomarkers can be classified into target, mechanistic, or outcome with varying degrees of linkage to disease or treatment effect. They can be used to determine proof of concept by characterising the efficacy or safety profiles, or determining differentiation from any competitor drugs. PK/PD modelling of biomarker data for novel and marketed compounds can be used to predict outpatient dose response. Subsequent simulations may replace or reduce the size and cost of larger phase 2b outpatient studies. Two examples of biomarkers and PK/PD modelling used to characterise dose response are presented. Penile plethysmography (RigiScan Plus) in male erectile dysfunction and phenylephrine challenge urethral pressure in benign prostatic hyperplasia are used to reduce time and cost to reach major exploratory development decision points in these indications.
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References
Boolell M, Gepi-Attee S, Gingell JC et al (1996) Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 78:257–261
Diamond LE, Earle DC, Rosen RC et al (2004) Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res 16:51–59
Furlow WL (1985) Prevalence of impotence in the United States. Med Aspects Hum Sex 19:13–16
Grabowski H (2004) Are the economics of pharmaceutical research and development changing? Productivity, Patents and political pressures. Pharmacoeconomics 22[Suppl 2]:15–24
Heaton JPW, Morales A, Adams MA et al (1995) Recovery of erectile function by the oral administration of apomorphine. Urology 45:200–206
Heaton JPW (2000) Apomorphine: an update of clinical trial results. Int J Impot Res 12[Suppl 4]:S67–S73
Kaiser FE (1999) Erectile dysfunction in the aging man. Med Clin N Am 83:1267–1278
Kaneko S, Bradley WE (1986) Evaluation of erectile dysfunction with continuous monitoring of penile rigidity. J Urol 136:1026–1029
NIH Consensus Conference (1993) Impotence. NIH Consensus Development Panel on Impotence. JAMA 270:83–90
Ogrinc FG, Linet OI (1995) Evaluation of real-time RigiScan monitoring in pharmacological erection. J Urol 154:1356–1359
Porst H (2002) IC351 (tadalafil, Cialis): update on clinical experience. Int J Impot Res 14[Suppl 1]:S57–S64
Pryor J (2002) Vardenafil: update on clinical experience. Int J Impot Res 14[Suppl 1]:S65–S69
Sultana SR, Murray K, Craggs MD et al (1998) Alpha, adrenoceptor antagonist selectivity determined by simultaneous blood pressure and long-term urethral pressure monitoring in men. Br J Clin Pharmacol 45:192
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© 2007 Springer-Verlag Berlin Heidelberg
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Sultana, S.R., Marshall, S., Davis, J., Littman, B.H. (2007). Experiences with Dose Finding in Patients in Early Drug Development: The Use of Biomarkers in Early Decision Making. In: Venitz, J., Sittner, W. (eds) Appropriate Dose Selection — How to Optimize Clinical Drug Development. Ernst Schering Research Foundation Workshop, vol 59. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-49529-1_5
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DOI: https://doi.org/10.1007/978-3-540-49529-1_5
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-27867-2
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