TABLE 1.

Comparison of model‐predicted and observed arithmetic mean PK parameter values for olanzapine and samidorphan after a single dose of OLZ/SAM 5 mg/10 mg in healthy control subjects with normal hepatic function and subjects with moderate hepatic impairment (model validation)

Parameter	Olanzapine					Samidorphan
	Cmax, ng/ml	Tmax,a h	AUCinf, ng h/ml	t½, h	CL/F, L/h	Cmax, ng/ml	Tmax, a h	AUCinf, ng h/ml	t½, h	CL/F, L/h
Single dose of OLZ/SAM 5 mg/10 mg in healthy controls with normal hepatic function
Predicted mean (n = 100)	4.9	6.1	243	31.0	24.2	33.9	0.9	286	12.7	37.5
Range of predicted mean across virtual trials (n = 10)	3.8–5.7	6.0–8.6	200–297	26.7–37.0	19.4–29.0	30.9–37.4	0.9–1.0	243–321	11.7–13.8	33.9–45.0
Observed mean (n = 10)12	4.9	7.0	275	51.9	22.2	30.8	1.0	263	9.0	39.8
Range (n = 10)	3.0–7.4	2.0–12.0	146–620	33.5–96.3	8.1–34.2	19.1–42.8	0.5–3	199–412	7.9–10.3	24.3–50.3
Ratio of predicted to observed	1.00	0.87	0.89	0.60	1.09	1.10	0.91	1.09	1.42	0.94
Single dose of OLZ/SAM 5 mg/10 mg in subjects with moderate hepatic impairment
Predicted mean (n = 100)	5.8	1.6	378	47.3	16.6	55.6	0.5	527	14.9	21.7
Range of predicted mean across virtual trials (n = 10)	4.1–7.0	1.3–2.4	290–516	37.8–58.8	12.0–22.2	50.1–60.3	0.5–0.6	397–623	13.0–16.9	17.3–32.0
Observed mean (n = 10)12	10.6	1.5	424	53.3	12.2	50.7	0.5	408	11.9	25.5
Range (n = 10)	5.3–17.7	0.5–4	311–547	37.3–95.3	9.14–16.1	31.4–71.3	0.5–1	309–550	8.8–15.3	18.2–32.4
Ratio of predicted to observed	0.54	1.06	0.89	0.91	1.36	1.10	1.01	1.29	1.25	0.85

Abbreviations: AUC_inf, area under the concentration‐time curve from 0 to infinity; CL/F, apparent total clearance of the compound from plasma after oral administration; C_max, maximum plasma concentration; OLZ/SAM, combination of olanzapine and samidorphan; PK, pharmacokinetic; t_½, elimination half‐life; T_max, time to maximum plasma concentration.

^a Median.