TABLE 7.

Day 14 pharmacokinetic parameters in the phase 1b MAD study^a

LHF-535 dose (mg/kg)	Statistic	Cmax (ng/mL)	Tmax (h)	AUC0–τ (h · ng/mL)	Cavg (ng/mL)	AUC0–∞ (h · ng/mL)	t1/2 (h)	CL/FSS (L/h)	VZ/F (L)
450 mgb	Mean	3,310	2	45,105	1,879	167,128	51	10	777
	SD	792	1	13,396	558	42,101	7	3	368
	CV (%)	24	37	30	30	25	14	32	47
	Median	2,934	2	44,059	1,836	169,744	49	10	679
900 mg	Mean	6,908	3	97,191	4,050	335,465	46	9	613
	SD	1,802	1	12,913	538	98,892	12	1	116
	CV (%)	26	37	13	13	29	25	13	19
	Median	6,560	3	95,312	3,971	353,298	51	9	623
1,125 mgc	Mean	7,544	2	108,028	4,501	281,353	58	16	1,287
	SD	2,122	1	52,485	2,187	85,112	13	2	103
	CV (%)	28	34	49	49	30	23	15	8
	Median	8,197	2	87,082	3,628	281,353	58	16	1,287

^aAll treatment groups comprised 6 participants. CL/F_SS, total body clearance at steady state as calculated by dose/AUCτ.

^bOne subject from the first cohort (450 mg) was excluded from all summary statistics due to not receiving all 14 doses. A second subject from this cohort was excluded from the calculation of AUC_0–∞, t_1/2, CL/F_SS, and V_Z/F (n = 4 instead of n = 5) due to a lack of plasma concentrations to accurately define the terminal phase.

^cParticipants in the 1,125-mg group received a loading dose of 2,250 mg once on day 1, followed by a maintenance dose of 1,125 mg/day on days 2 through 14. Four subjects from this cohort (1,125 mg) were excluded from the calculation of AUC_0–∞, t_1/2, CL/F_SS, and V_Z/F (n = 2 instead of n = 6) due to a lack of plasma concentrations to accurately define the terminal phase.