Dose-finding studies

Staessen JA, Kuznetsova T, Acceto R et al (2005) OASIS-HT design of a pharmacogenomic dose-finding study. Pharmacogenomics 6 755-775... 

A dose-finding study of duloxetine based on duloxetine-associated SERT occupancy was recently reported using PET [61]. SERT occupancies increased dose responsively and correlated well with the plasma concentration of duloxetine. It was found that 40 mg or more duloxetine was needed to attain 80% occupancy, and 60 mg of duloxetine could maintain a high level of SERT occupancy with once-a-day dosing. 

Schmidt R. Dose-finding studies in cUnical drug development. Eur J Clin Pharmacol 1988 34 15-19. 

Senn SJ. Cross-over, Sequential and Dose Finding Studies. Statistical Issues in Drug Development. Chichester John Wiley, 1997 237-9 257-64 275-7. 

Fujii M, Nameki H, Kawaura M, et al. A dose finding study of carboplatin (CBDCA) + UFT in head and neck cancer. ProcAm Soc Clin Oncol 1998 18 406a (abstr 1564). 

Available pharmacokinetic (PK) studies of medications with potential to treat pediatric anxiety disorders have been open studies that examine PK parameters and monitor adverse effects in children and adolescents. None of the pediatric PK studies described below were designed as dose finding studies, and none of the studies were able to describe a clear association between dose or exposure and specific adverse effect. However, pediatric PK data can be useful to guide dosing and adverse effect monitoring to the extent that the weight-adjusted PK parameters inform extrapolation based on comparable studies of adult PK. The following summary of PK studies is based on multiple-dose PK studies. 

Martin CW, Riley SC, Everington D, Groome NP, Riemersma RA, Baird DT, Anderson RA. Dose-finding study of oral desogestrel with testosterone pellets for suppression of the pituitary-testicular axis in normal men. Hum Reprod 2000 15(7) 1515-24. 

Toogood AA, Shalet SM. Growth hormone replacement therapy in the elderly with hypothalamic-pituitary disease a dose-finding study. J Clin Endocrinol Metab 1999 84(l) 131-6. 

PK data for cetuximab were derived from 19 clinical studies performed up to 2003 [16]. Ten of these studies were conducted as dose-escalation/dose-finding studies, while the remaining nine were conducted at the approved dosing regimen of 400 mg/m2 initially, followed by weekly doses of 250 mg/m2. 

Optimizing the Design of Phase II Dose Finding Studies... 

Tambaro, R., Greggi, S., Iaffaioli, R. V., Rossi, A., Pisano, C., Manzione, L., Ferrari, E., Di Maio, M., Iodice, F., Casella, G., Laurelli, G., and Pignata, S. (2003), An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer,Ann. Oncol., 14,1406-1411. 

Goff DC, Posever T, Herz L, Simmons J, Kletti N, Lapierre K, Wilner KD, Law CG, Ko GN. An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol 1998 18(4) 296—304. 

Trepo, C., Jezek, P., Atkinson, G., Boon, R., Young, C. Famciclovir in chronic hepatitis B results of a dose-finding study. J. Hepatol. 2000 32 1011-1018... 

Jorga, K. Fotteler, B. Banken, L. Snell, P. Steimer, J.L. Population pharmacokinetics of tolcapone in parkinsonian patients in dose finding studies. Br. J. Clin. Pharmacol. 

In a dose-finding study with bosentan (100,500,1000, and 2000 mg/day) in 293 hjrpertensive patients (5) there were statistically significant falls in diastolic blood pressure with the 500 and 2000 mg/day doses. The effects were similar to that of enalapril 20 mg/day. The lowering of blood pressure was not associated with any changes in heart rate, plasma noradrenaline concentrations, plasma renin activity, or angiotensin II concentrations. 

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