Table 2.

Summary of single-dose PK parameters of pevonedistat and statistical analysis of effects of rifampin on pevonedistat PK (PK population)

	N	Cmax (ng/mL) geometric mean (CV)	AUClast (h*ng/mL) geometric mean (CV)	AUC∞ (h*ng/mL) geometric mean (CV)	t1/2z (h)mean (SD)	CL (L/h) geometric mean (CV)	Vss (L) geometric mean (CV)
In the absence of rifampin (Day 1)	20	601.7 (52.5%)	2988 (55.9%)	3030 (55.3%)	7.4 (1.4)	33.1 (31.2%)	277.8 (46.2%)
In the presence of rifampin (Day 10)	17	564.1 (53.9%)	2328 (65.6%)	2374 (64.3%)	5.7 (1.4)	41.5 (28.8%)	264.6 (46.0%)

		Cmax (ng/mL)		AUClast (h*ng/mL)		AUC∞ (h*ng/mL)
		N	LS mean	N	LS mean	N	LS mean
In the absence of rifampin		20	601.7	20	2988	20	3030
In the presence of rifampin		17	579	17	2345	17	2393
LS mean ratio (90% CI)		0.962 (0.792–1.17)		0.785 (0.684–0.901)		0.790 (0.692–0.902)

Estimates for each PK parameter were obtained using a mixed-effects model of log (PK parameter) with fixed terms for the rifampin effect and random terms for patient. The CIs are calculated for the difference in the LS means of the ln-transformed AUC_last, AUC_∞, or C_max values (difference: C1D10-C1D1). Antilogs of the confidence limits for the difference are taken to construct the CIs for the ratio of the geometric means. All parameters presented are in the original scale

AUC_last area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration, AUC_∞ area under the plasma concentration-time curve from time 0 extrapolated to infinity, CL plasma clearance, C_max observed maximum plasma concentration, CV coefficient of variation, max maximum, min minimum, PK pharmacokinetic, t_1/2z terminal half-life, V_ss volume of distribution at steady-state, LS least squares