Table 4.

Summary of ARO-ANG3 plasma pharmacokinetic parameters after a subcutaneous injection of ARO-ANG3 in HPs (day 1 SAD cohorts; days 1 and 29 MAD cohorts)

	Dose	Cmax (ng ml−1)	Tmax (h)	AUClast (h × ng ml−1)	AUCinf (h × ng ml−1)	t1/2 (h)	CL/F (l h−1)	Vz/F (l)
SAD (dose 1, day 1)	35 mg	49.6 ± 17.5; 6	6.0 (6.0–9.2); 6	651 ± 161; 6	682 ± 156; 6	4.5 ± 1.4; 6	53.6 ± 12.2; 6	356 ± 151;
	100 mg	222 ± 82.3; 6	6.0 (6.0–9.0); 6	3,060 ± 1,040; 6	3,180 ± 1,120; 6	4.5 ± 1.0; 6	34.4 ± 10.5; 6	221 ± 72.3; 6
	200 mg	368 ± 254; 6	9.0 (0.5–12.1); 6	6,060 ± 3,160; 6	6,220 ± 3,050; 6	6.6 ± 4.6; 6	36.4 ± 10.6; 6	368 ± 309; 6
	300 mg	635 ± 214; 6	10.5 (6.0–18.0); 6	11,600 ± 3,360; 6	11,200 ± 3,510; 5	4.8± 1.4; 5	29.0 ± 9.30; 5	193 ± 53.6; 5
MAD (dose 1, day 1)	100 mg	273 ± 100; 4	7.5 (3.0–9.0); 4	3,310 ± 792; 4	3,020 ± 379; 3	3.9 ± 1.1; 3	33.4 ± 4.05; 3	182 ± 39.3; 3
	200 mg	583 ± 187; 4	10.5 (2.0–18.0); 4	8,870 ± 689; 4	8,910± 688; 4	5.0 ± 0.8; 4	22.6 ± 1.75; 4	162 ± 32.2; 4
	300 mg	779 ± 452; 4	9.0 (9.0–18.0); 4	12,400 ± 4,100; 4	14,000 ± 3,270; 3	5.3 ± 1.0; 3	22.2 ± 4.58; 3	175± 64.7; 3
MAD (dose 2, day 29)	100 mg	256 ± 55.3; 4	6.0 (6.0–6.0); 4	3,290± 612; 4	3,370 ± 564; 4	4.6 ± 0.6; 4	30.2 ± 4.59; 4	198 ± 34.7; 4
	200 mg	596 ± 81.7; 4	6.0 (3.0–9.0); 4	9,210 ± 777; 4	9,240± 777; 4	4.9 ± 0.3; 4	21.8 ± 1.83; 4	155 ± 19.1; 4
	300 mg	745 ± 438; 4	7.5 (1.0–9.0); 4	12,500 ± 3,650; 4	14,100 ± 2,550; 3	5.5 ± 1.4; 3	21.7 ± 3.60; 3	177 ± 63.7; 3

C_max, maximum observed plasma concentration; AUC_last, area under the plasma concentration versus time curve from the zero to the last quantifiable plasma concentration; AUC_inf, area under the plasma concentration versus time curve from zero to infinity; CL/F, plasma clearance; Vz/F, terminal-phase volume of distribution.

Note: T_max is presented as median (minimum–maximum); n; all other parameters are presented as arithmetic mean ± s.d.; n.

As noted in the Methods, pharmacokinetic parameters were evaluated in HP cohorts only.