Liquid chromatography-mass spectrometry using turbo electrospray ionization in multi-reaction monitoring mode was performed in order to quantify the concentration of Org 26576. The assay has been validated over the range of 0.2–200 ng/mL. Both trials utilized the same bioanalytic approach and followed the same standard operating procedures. Laboratory assessments were conducted in full compliance with Good Laboratory Practice. Statistical Analysis Safety and Tolerability All endpoints for both studies were analyzed using the

all-subjects-treated population (participants who took at least one dose of the study medication). Descriptive statistics were calculated; however, Tozasertib supplier no statistical testing was performed. Pharmacokinetics In study 1, group 3, a one-way analysis of variance (ANOVA) with a ‘Food’ factor and repeated measures for each subject on food was applied to the parameters pertaining to treatment with CYC202 research buy and without food (i.e. the Selleckchem LB-100 maximum plasma drug concentration [Cmax] during

a dosage interval at steady state [Cmax,ss], the time to reach Cmax [tmax] following drug administration at steady state [tmax,ss], and the area under the plasma concentration-time curve [AUC] from 0 to 12 hours at steady state [AUC12,ss]), which were compared by means of a one-way ANOVA with a ‘Food’ factor and repeated measures for each subject on food (i.e. a paired t-test). Food-independent pharmacokinetics were to be concluded if the food effect for all parameters analyzed was not significant. An analogous analysis was applied to explore the presence of a regimen effect (100 mg single dose on day 1, versus 100 mg bid on day 9). For this purpose, parameters pertaining to single dosing (i.e. Cmax, tmax, the elimination half-life [t1/2], and the AUC from time zero to infinity [AUC∞]) and to steady

state (i.e. Cmax,ss, tmax,ss, t1/2,ss, and AUC∞,ss) were compared. Time-independent pharmacokinetics were to be concluded if the regimen effect Selleckchem Pomalidomide for all parameters analyzed was not significant. In group 4, the parameters (i.e. the dose-normalized [dn] Cmax,ss [dn-Cmax,ss], tmax,ss, and dn-AUC12,ss) pertaining to the escalating multiple dosing (100, 225, 325, and 400 mg) were compared by means of a two-way ANOVA with fixed factors of ‘Dose’ and ‘Subject’. If there was no significant dose effect, then the pharmacokinetics were to be considered as linear within the dose range studied. In study 2, the Org 26576 pharmacokinetic parameters in part II (i.e. dn-Cmax, t1/2, dn-AUC, and tmax) were compared by means of an ANOVA with fixed factors of ‘Dose’ (low dose: Org 26576 100 mg bid group; high dose: Org 26576 400 mg bid group), ‘Day’ (1, 4, 27), ‘Dose*Day’ interaction, and repeated measures for each subject (subject nested within dose). In both studies, loge-transformed values of the parameters were used in the ANOVAs, except for tmax, for which a Wilcoxon signed rank test was performed.