Table III.

Comparison of Simulated (SIM) vs. Observed (OBS) Mean Plasma PK Parameters of NVS123 in Humans

Parameters	F1 (Arm 1)		F1 (Arm 2)		F2		F3
	OBS	SIM	OBS	SIM	OBS	SIM	OBS	SIM
Dose (mg)
Fasted	200	200	200	200	200	200	200	200
Fed
C max (ratio)
Fed vs. fasted	1.76	2.03	1.72	2.05	1.38	1.53	1.38	1.66
FE of predictiona	1.16		1.19		1.11		1.21
AUC0–inf (ratio)
Fed vs. Fasted	1.57	1.84	1.58	1.84	1.33	1.51	1.37	1.57
FE of predictiona	1.17		1.17		1.13		1.15
t max (ratio)
Fed vs. fasted	1.50	1.91	1.50	1.80	1.25	2.25	1.50	2.06
FE of predictiona	1.27		1.20		1.80		1.38
F a (%)
Fasted	N/A	34.7	N/A	34.7	N/A	43.9	N/A	38.5
Fed	N/A	64.0	N/A	64.0	N/A	65.7	N/A	59.9
F (%)
Fasted	N/A	32.1	N/A	32.3	N/A	40.5	N/A	35.9
Fed	N/A	59.2	N/A	59.7	N/A	60.7	N/A	55.8
Precipitation time (s)b
Fasted	N/A	1,000	N/A	1,000	N/A	1,800	N/A	1,500
Fed	N/A	3,500	N/A	3,500	N/A	3,000	N/A	3,000
Correlation coefficient (R 2)c
Fasted	N/A	0.95	N/A	0.93	N/A	0.97	N/A	0.96
Fed	N/A	0.93	N/A	0.91	N/A	0.93	N/A	0.92
Root mean squared prediction error (RMSE)d
Fasted	N/A	28.3	N/A	32.8	N/A	30.4	N/A	28.2
Fed	N/A	81.3	N/A	71.8	N/A	81.4	N/A	84.5

^aFold error (FE) of the prediction. $\mathrm{FE}={10}^{\left|\mathrm{Log}\left(\frac{\mathrm{Predicted}}{\mathrm{Observed}}\right)\right|}$

^bPrecipitation time (T _p) in the human model was assumed to be similar to that in the dog model because of relatively similar intestinal pH and bile salt concentration. This assumption was verified by comparison of simulated and observed PK profiles (Fig. 3) and parameters (Table III)

^cCorrelation coefficient between the observed concentration and simulated values

^dRoot mean squared prediction error (RMSE) of plasma concentration. RMSE = $\sqrt{{\displaystyle \sum {\left(\mathrm{SIM}-\mathrm{OBS}\right)}^2/N}}$ where N is the number of observed data points