The use of biomarkers in human pharmacology (Phase I) studies

Annual Review of Pharmacology and Toxicology

Volumn 55, Issue , 2015, Pages 55-74

  Cohen, A F ^a,b   Burggraaf, J ^a,c   Van Gerven, J M A ^a,b   Moerland, M ^a   Groeneveld, G J ^a,d  

^a CENTRE FOR HUMAN DRUG RESEARCH   (Netherlands)

^b LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^c LEIDEN UNIVERSITY   (Netherlands)

^d VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Clinical trials; Precision medicine; Prediction in pharmacology; Question based drug development; Surrogate endpoints

Indexed keywords

BIOLOGICAL MARKER; PHARMACOLOGICAL BIOMARKER;

CLINICAL STUDY; DRUG DEVELOPMENT; HUMAN; METHODOLOGY; PATHOPHYSIOLOGY; PHASE 1 CLINICAL TRIAL (TOPIC); PLANNING; PRIORITY JOURNAL; REVIEW; ANIMAL; BIOASSAY; DOSE CALCULATION; DOSE RESPONSE; DRUG EFFECTS; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; PATIENT SAFETY; PHARMACOKINETICS; PHARMACOLOGY; PROCEDURES; RISK ASSESSMENT; RISK FACTOR; SIGNAL TRANSDUCTION;

ANIMALS; BIOMARKERS, PHARMACOLOGICAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; DRUG DOSAGE CALCULATIONS; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; ENDPOINT DETERMINATION; HUMANS; PATIENT SAFETY; PHARMACOKINETICS; PHARMACOLOGY; RISK ASSESSMENT; RISK FACTORS; SIGNAL TRANSDUCTION;

EID: 84920855916     PISSN: 03621642     EISSN: 15454304     Source Type: Book Series    
DOI: 10.1146/annurev-pharmtox-011613-135918     Document Type: Review

References (81)

1. Black JW, Crowther AF, Shanks RG, Belf MD, Smith LH, et al. 1964. A new adrenergic: beta-receptor antagonist. Lancet 283:1080-81
2. Pilkington TRE, Lowe RD, Robinson BF, Titterington E. 1962. Effect of adrenergic blockade on glucose and fatty-acid mobilisation in man. Lancet 280:316-17
3. Dornhorst AC, Robinson BF. 1962. Clinical pharmacology of a beta-adrenergic-blocking agent (nethalide). Lancet 280:314-16
4. Prichard BNC, Gillam PMS. 1969. Treatment of hypertension with propranolol. BMJ 1:7-16
5. Harris WS, Schoenfeld CD, Brooks RH, Weissler AM. 1966. Effect of beta adrenergic blockers on the hemodynamic responses to epinephrine in man. Am. J. Cardiol. 17:484-92
6. Cohen AF. 2010. Developing drug prototypes: pharmacology replaces safety and tolerability? Nat. Rev. Drug Discov. 9(11):856-65
7. Nissen SE, Tardif J-C, Nicholls SJ, Revkin JH, Shear CL, et al. 2007. Effect of torcetrapib on the progression of coronary atherosclerosis. N. Engl. J. Med. 356:1304-16
8. Clark RW, Sutfin TA, Ruggeri RB, Willauer AT, Sugarman ED, et al. 2004. Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib. Arterioscler. Thromb. Vasc. Biol. 24:490-97
9. Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, et al. 2007. Torcetrapib and carotid intimamedia thickness in mixed dyslipidaemia (RADIANCE 2 study): A randomised, double-blind trial. Lancet 370:153-60
10. Forrest MJ, Bloomfield D, Briscoe RJ, Brown PN, Cumiskey A-M, et al. 2008. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br. J. Pharmacol. 154(7):1465-73
11. McKenney JM, Davidson MH, Shear CL, Revkin JH. 2006. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels on a background of atorvastatin. J. Am. Coll. Cardiol. 48(9):1774-81
12. Barter P, Caulfield M. 2007. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357(21):2109-22
13. Zhao L, Jin W, Rader D, Packard C, Feuerstei N. 2009. A translational medicine perspective of the development of torcetrapib:Does the failure of torcetrapib development cast a shadow on future development of lipid modifying agents, HDLelevation strategies or CETP as a viable molecular target for atherosclerosis? Biochem. Pharmacol. 78:315-25
14. Kenter MJH, Cohen AF. 2006. Establishing risk of human experimentation with drugs: lessons from TGN1412. Lancet 368(9544):1387-91
15. Yusuf S, Flather M, Gent M. 1997. Effects of RheothRx on mortality, morbidity, left ventricular function, and infarct size in patients with acute myocardial infarction. Circulation 96(1):192-201
16. Schaer GL, Spaccavento LJ, Browne KF, Krueger KA, Krichbaum D, et al. 1996. Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction: results of a randomized, double-blind, placebo-controlled trial. Circulation 94(3):298-307
17. Jewell RC, Khor SP, Kisor DF, LaCroix KA, Wargin WA. 1997. Pharmacokinetics of RheothRx injection in healthy male volunteers. J. Pharm. Sci. 86(7):808-12
18. Eur. Parliam. Counc. 2001. Directive 2001/20/EC of the European Parliament and of the Council. Off. J. Eur. Communities L121:34-44
19. Ng R. 2009. Drugs: From Discovery to Approval. Hoboken, NJ: Wiley. 2nd ed.
20. Eur. Med. Agency. 1998. Note for guidance on general considerations for clinical trials (CPMP/ICH/291/95). Rep., London
21. Lenfle S, Loch C. 2009. Lost roots: how project management settled on the phased approach (and compromised its ability to lead change in modern enterprises). INSEADWork. Pap., Fontainebleau, France
22. De Meyer A, Loch CH, Pich MT. 2002. Managing project uncertainty: from variation to chaos. IEEE Eng. Manag. Rev. 30:91-98
23. Cohen A. 2007. Should we tolerate tolerability as an objective in early drug development? Br. J. Clin. Pharmacol. 64(3):249-52
24. Sheiner L. 1997. Learning versus confirming in clinical drug development. Clin. Pharmacol. Ther. 61(3):275-91
25. Danhof M, Alvan G, Dahl SG, Kuhlmann J, Paintaud G. 2005. Mechanism-based pharmacokineticpharmacodynamic modeling- A new classification of biomarkers. Pharm. Res. 22(9):1432-37
26. Lalonde RL, Kowalski KG, Hutmacher MM, Ewy W, Nichols DJ, et al. 2007. Model-based drug development. Clin. Pharmacol. Ther. 82(1):21-32
27. Milligan PA, Brown MJ, Marchant B, Martin SW, van der Graaf PH, et al. 2013. Model-based drug development: A rational approach to efficiently accelerate drug development. Clin. Pharmacol. Ther. 93(6):502-14
28. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, et al. 2014. Mortality and morbidity in patients receiving encainide, flecainide or placebo-the Cardiac Arrhythmia Suppression Trial. N. Engl. J. Med. 324:781-88
29. Dei Cas L, Manca C, Bernardini B, Vasini G, Visioli O. 1982. Noninvasive evaluation of the effects of oral ibopamine (SB 7505) on cardiac and renal function in patients with congestive heart failure. J. Cardiovasc. Pharmacol. 4:436-40
30. Col J, Mievis E, Reynaert M. 1983. Ibopamine in very severe congestive heart failure: pilot haemodynamic invasive assessment. Eur. J. Clin. Pharmacol. 24(3):297-300
31. van Veldhuisen DJ, Man int Veld AJ, Dunselman PHJM, Lok DJA, Dohmen HJM, et al. 1993. Doubleblind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT). J. Am. Coll. Cardiol. 22(6):1564-73
32. Hampton JR, van Veldhuisen DJ, Kleber FX, Cowley AJ, Ardia A, et al. 1997. Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Lancet 349:971-77
33. Yee KM, Struthers A. 1997. Can drug effects on mortality in heart failure be predicted by any surrogate measure? Eur. Heart J. 18(12):1860-64
34. Ho D, Moudgil T, Alam M. 1989. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N. Engl. J. Med. 321(24):1621-25
35. Atkinson AJ Jr, Colburn WA, DeGruttola VG, DeMets DL, Downing GJ, et al. 2001. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69(3):89-95
36. Peto R, Pike M, Armitage P, Breslow N, Cox D, et al. 1976. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Br. J. Cancer 34:585-612
37. U. S. Food Drug Adm. 2004. Innovation or stagnation: challenge and opportunity on the critical path to new medical products. Chall. Oppor. Rep., U. S. Dep. Health Hum. Serv., Rockville, MD
38. U. S. Food Drug Adm. 2011. Guidance for industry: E16 biomarkers related to drug or biotechnology product development: context, structure and format of qualification submissions. Rep., U. S. Dep. Health Hum. Serv., Rockville, MD
39. U. S. Food Drug Adm. 2005. Guidance for industry: pharmacogenomic data submissions. Proced. Rep., U. S. Dep. Health Hum. Serv., Rockville, MD
40. Lee JW, Devanarayan V, Barrett YC, Weiner R, Allinson J, et al. 2006. Fit-for-purpose method development and validation for successful biomarker measurement. Pharm. Res. 23(2):312-28
41. Expert Sci. Group. 2006. Expert scientific group on phase one clinical trials. Final Rep., Nov. 30
42. Appel S, Kumle A, Hubert M, Duvauchelle T. 1997. First pharmacokinetic-pharmacodynamic study in humans with a selective 5-hydroxytryptamine4 receptor agonist. J. Clin. Pharmacol. 37:229-37
43. Wood P. 2012. Tegaserod in the treatment of constipation-predominant irritable bowel syndrome. Do the risks outweigh the benefits? Naunyn-Schmiedebergs Arch. Pharmacol. 385(1):1-3
44. Al-Judaibi B, Chande N, Gregor J. 2010. Safety and efficacy of tegaserod therapy in patients with irritable bowel syndrome or chronic constipation. Can. J. Clin. Pharmacol. 17(1):e194-200
45. Chan KY, de Vries R, Leijten FPJ, Pfannkuche H-J, van den Bogaerdt AJ, et al. 2009. Functional characterization of contractions to tegaserod in human isolated proximal and distal coronary arteries. Eur. J. Pharmacol. 619(1-3):61-67
46. Tack J, Camilleri M, Chang L, Chey WD, Galligan JJ, et al. 2012. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders. Aliment. Pharmacol. Ther. 35(7):745-67
47. de Visser S. 2003. A question based approach to drug development. PhD Thesis, Leiden Univ., Leiden, Neth.
48. Morgan P, Van Der Graaf PH, Arrowsmith J, Feltner DE, Drummond KS, et al. 2012. Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival. Drug Discov. Today 17(9-10):419-24
49. Copeland TE, Keenan PT. 1998. Making real options real. McKinsey Q. 3:128-42
50. DSouza F. 2002. Putting real options to work to improve project planning. Harvard Manag. Update 7(8):3-6
51. Aronson JK, Ferner RE. 2003. Joining the DoTS: new approach to classifying adverse drug reactions. BMJ 327:1222-25
52. van der Post JP, de Visser SJ, Schoemaker RC, Cohen AF, van Gerven JMA. 2004. Pharmacokinetic/pharmacodynamic assessment of tolerance to central nervous system effects of a 3 mg sustained release tablet of rilmenidine in hypertensive patients. J. Psychopharmacol. 18(2):221-27
53. Hoever P, Hay J, Rad M, Cavallaro M, van Gerven JM, Dingemanse J. 2013. Tolerability, pharmacokinetics, and pharmacodynamics of single-dose almorexant, an orexin receptor antagonist, in healthy elderly subjects. J. Clin. Psychopharmacol. 33(3):363-70
54. Van Poelgeest EP, Swart RM, Betjes MGH, Moerland M, Weening JJ, et al. 2013. Acute kidney injury during therapy with an antisense oligonucleotide directed against PCSK9. Am. J. Kidney Dis. 62(4):796-800
55. Lee JW, Weiner RS, Sailstad JM, Bowsher RR, Knuth DW, et al. 2005. Method validation and measurement of biomarkers in nonclinical and clinical samples in drug development: A conference report. Pharm. Res. 22(4):499-511
56. van der Graaf PH. 2012. CPT: pharmacometrics and systems pharmacology. CPT Pharmacometrics Syst. Pharmacol. 1:e8
57. van Meer L, Moerland M, Cohen AF, Burggraaf J. 2013. Urinary kidney biomarkers for early detection of nephrotoxicity in clinical drug development. Br. J. Clin. Pharmacol. 77:947-57
58. de Visser SJ, van der Post JP, deWaal PP, Cornet F, Cohen AF, van Gerven JMA. 2003. Biomarkers for the effects of benzodiazepines in healthy volunteers. Br. J. Clin. Pharmacol. 55(1):39-50
59. de Visser SJ, van der Post JP, Pieters MSM, Cohen AF, van Gerven JMA. 2001. Biomarkers for the effects of antipsychotic drugs in healthy volunteers. Br. J. Clin. Pharmacol. 51:119-32
60. Zuurman L, Ippel AE, Moin E, van Gerven JMA. 2009. Biomarkers for the effects of cannabis and THC in healthy volunteers. Br. J. Clin. Pharmacol. 67(1):5-21
61. Dumont GJH, de Visser SJ, Cohen AF, van Gerven JMA. 2005. Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in healthy subjects. Br. J. Clin. Pharmacol. 59(5):495-510
62. Zoethout RWM, Delgado WL, Ippel AE, Dahan A, van Gerven JMA. 2011. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers. Br. J. Clin. Pharmacol. 71(3):331-50
63. Rijnbeek B, de Visser SJ, Franson KL, Cohen AF, vanGerven JMA. 2003. REMsleep effects as a biomarker for the effects of antidepressants in healthy volunteers. J. Psychopharmacol. 17(2):196-203
64. Pleuvry BJ, Maddison SE, Odeh RB, Dodson ME. 1980. Respiratory and psychological effects of oral temazepam in volunteers. Br. J. Anaesth. 52(9):901-6
65. van Steveninck AL, Schoemaker HC, Pieters MSM, Kroon R, Breimer DD, Cohen AF. 1991. A comparison of the sensitivities of adaptive tracking, eye movement analysis and visual analog lines to the effects of incremental doses of temazepam in healthy volunteers. Clin. Pharmacol. Ther. 50(2):172-80
66. Khalili-Mahani N, van Osch MJP, Baerends E, Soeter RP, de Kam M, et al. 2011. Pseudocontinuous arterial spin labeling reveals dissociable effects of morphine and alcohol on regional cerebral blood flow. J. Cereb. Blood Flow Metab. 31(5):1321-33
67. van der Post J, de Waal PP, de Kam ML, Cohen AF, vanGerven JMA. 2004. No evidence of the usefulness of eye blinking as a marker for central dopaminergic activity. J. Psychopharmacol. 18(1):109-14
68. Strougo A, Zuurman L, Roy C, Pinquier JL, van Gerven JMA, et al. 2008. Modelling of the concentration- effect relationship of THC on central nervous system parameters and heart rate-insight into its mechanisms of action and a tool for clinical research and development of cannabinoids. J. Psychopharmacol. 22(7):717-26
69. de Haas SL, de Visser SJ, van der Post JP, de Smet M, Schoemaker RC, et al. 2007. Pharmacodynamic and pharmacokinetic effects of TPA023, a GABAA β2, 3 subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers. J. Psychopharmacol. 21(4):374-83
70. Chen X, de Haas S, de Kam M, van Gerven J. 2012. An overview of the CNS-pharmacodynamic profiles of nonselective and selective GABA agonists. Adv. Pharmacol. Sci. 2012:134523
71. Liem-Moolenaar M, Zoethout RWM, de Boer P, Schmidt M, de Kam ML, et al. 2010. The effects of the glycine reuptake inhibitor R213129 on the central nervous system and on scopolamine-induced impairments in psychomotor and cognitive function in healthy subjects. J. Psychopharmacol. 24(11):1671-79
72. Klumpers LE, Fridberg M, de Kam ML, Little PB, Jensen NO, et al. 2013. Peripheral selectivity of the novel cannabinoid receptor antagonist TM38837 in healthy subjects. Br. J. Clin. Pharmacol. 76(6):846-57
73. Zuurman L, Roy C, Schoemaker RC, Amatsaleh A, Guimaeres L, et al. 2010. Inhibition of THC-induced effects on the central nervous system and heart rate by a novel CB1 receptor antagonist AVE1625. J. Psychopharmacol. 24(3):363-71
74. Jacobs GE, van Gerven JMA, de Kam ML, Elassaiss-Schaap J, Ruigt G, et al. 2011. A pharmacological tool to assess vasopressinergic co-activation of the hypothalamus-pituitary-adrenal axis more integrally in healthy volunteers. J. Psychopharmacol. 25(3):361-69
75. Jacobs GE, Hulskotte EGJ, van Gerven JMA, Zuurman L, de Kam ML, et al. 2011. Desmopressin as a pharmacological tool in vasopressinergic hypothalamus-pituitary-adrenal axis modulation: neuroendocrine, cardiovascular and coagulatory effects. J. Psychopharmacol. 25(3):353-60
76. Smarius LJCA, Jacobs GE, Hoeberechts-Lefrandt DHM, de Kam ML, van der Post JP, et al. 2008. Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa. J. Psychopharmacol. 22(4):426-33
77. Kemme MJB, Burggraaf J, Schoemaker RC, Cohen AF, Blauw GJ. 2000. No evidence for functional involvement of 5-HT2B receptors in serotonin-induced vasodilatation in the human forearm. 36:699-703
78. Moerland M, Kemme M, Dijkmans A, Bergougnan L, Burggraaf J. 2011. Modulation of vasoactivity and platelet aggregation by selective 5-HT receptor antagonism in humans. 58:575-80
79. van Gerven JMA, Roncari G, Schoemaker RC, Massarella J, Keesmaat P, et al. 1997. Integrated pharmacokinetics and pharmacodynamics of Ro 48-8684, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects. Br. J. Clin. Pharmacol. 44(5):487-93
80. Weber O, Willmann S, Bischoff H, Li V, Vakalopoulos A, et al. 2012. Prediction of a potentially effective dose in humans for BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein (CETP) by allometric species scaling and combined pharmacodynamic and physiologically-based pharmacokinetic modelling. Br. J. Clin. Pharmacol. 73(2):219-31
81. Boettcher M-F, Heinig R, Schmeck C, Kohlsdorfer C, Ludwig M, et al. 2012. Single dose pharmacokinetics, pharmacodynamics, tolerability and safety of BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein. Br. J. Clin. Pharmacol. 73(2):210-18