TABLE 3.

Descriptive statistics for V-7404 plasma pharmacokinetic parameters for single ascending dose and multiple ascending doses administered once daily (pharmacokinetic assessment set)

Cohort/dose (mg)	Statisticc	AUC (ng · h/ml)a	Cmax (ng/ml)d	tmax (h)b	t1/2 (h)e	CL/F (liters/h)f	Vz/F (liters)g	Cavg (ng/ml)h	LIi	RAUCj	RCmaxk
Single ascending dose, fasted condition
1/200 (n = 4)	No. of patients	3	4	4	3	3	3
	GeoMean	77.42	83.35	0.5	0.3152	2,580	1,170
	GeoCV%	54.7	170.5	0.25, 1.50	4.1	54.8	50.7
2/500 (n = 4)	No. of patients	4	4	4	4	4	4
	GeoMean	277.1	366.6	0.25	0.8249	1,804	2,145
	GeoCV%	22.8	16.6	0.25, 0.25	61.3	22.7	60.7
4/1,000 (n = 4)	No. of patients	3	4	4	3	3	3
	GeoMean	591.9	436.6	0.38	1.017	1,688	2,475
	GeoCV%	53.8	55.2	0.25, 0.50	116	53.8	44.7
5/1,500 (n = 4)	No. of patients	3	4	4	3	3	3
	GeoMean	590.4	417	0.51	1.939	2,537	7,103
	GeoCV%	19.8	18.4	0.25, 0.77	95.9	19.9	85.5
6/2,000 (n = 4)	No. of patients	3	4	4	3	3	3
	GeoMean	1,098	636.8	0.63	2.336	1,823	6,148
	GeoCV%	21.2	18.8	0.25, 0.75	42.3	21.3	23.3
Single ascending dose, fed and fasted conditions (500 mg)
2/500 (n = 4), fasted	No. of patients	4	4	4	4	4	4
	GeoMean	277.1	366.6	0.25	0.8249	1,804	2,145
	GeoCV%	22.8	16.6	0.25, 0.25	61.3	22.7	60.7
3/500 (n = 4), fed	No. of patients	3	4	4	3	3	3
	GeoMean	139	124.7	1	0.6834	3,600	3,551
	GeoCV%	43.9	39.9	0.50, 1.50	29.7	43.8	79.5
Multiple ascending dose, day 1 QD
1/500 (n = 8)	No. of patients	8	8	8	8	8	8
	GeoMean	240.7	246.9	0.48	0.769	2,076	2,305
	GeoCV%	49.8	60.6	0.25, 0.75	69	49.6	69.9
2/1,000 (n = 8)	No. of patients	8	8	8	8	8	8
	GeoMean	649.8	580.4	0.5	1.618	1,540	3,596
	GeoCV%	35.3	37.7	0.25, 0.75	52.8	35.3	41.3
3/2,000 (n = 8)	No. of patients	3	8	8	3	3	3
	GeoMean	1075	938.9	0.5	3.845	1,860	10,320
	GeoCV%	45.3	38.3	0.25, 1.00	71.3	45.4	23
Multiple ascending dose, day 14 QD
1/500 (n = 8)	No. of patients	8	8	8	5	8	5	8	8	8	8
	GeoMean	302.4	370.2	0.25	1.414	1,656	3,022	12.58	1.254	1.258	1.499
	GeoCV%	32	36.3	0.25, 1.00	76	32.2	46.1	32.1	31	31	53.2
2/1,000 (n = 8)	No. of patients	8	8	8	7	8	7	8	8	8	8
	GeoMean	564.5	433	0.5	1.822	1,771	4,667	23.53	0.869	0.872	0.746
	GeoCV%	22.3	44.3	0.25, 0.53	104.5	22.3	95.5	22.4	20.1	20.1	42.6
3/2,000 (n = 8)	No. of patients	8	8	8	6	8	6	8	3	8	8
	GeoMean	961.6	789.7	0.5	4.186	2,081	11,460	40.02	0.7707	0.8168	0.8406
	GeoCV%	33.9	41.5	0.25, 0.75	58.6	33.9	61.7	33.9	23.9	19.5	33.7

^aArea under the plasma drug concentration-time curve (AUC) values are extrapolated to an infinite time (AUC_0–inf) for all groups except the multiple ascending dose, day 14 QD cohort, which is calculated over a dosing interval (AUC_0–tau). For this cohort, CL/F is also given as apparent clearance at steady state (CL_ss/F).

^bMedian, minimum, and maximum presented for time to maximum plasma concentration (t_max).

^cGeoCV%, geometric coefficient of variation; GeoMean, geometric mean; QD, once daily.

^dC_max, maximum concentration of drug in serum.

^et_1/2, terminal elimination half-life.

^fCL/F, apparent clearance.

^gV_z/F, apparent volume of distribution.

^hC_avg, average plasma concentration over a dosing interval.

ⁱLI, linearity index.

^jRAUC, accumulation ratio for AUC.

^kRC_max, accumulation ratio for C_max.