Table 2.
Summary of Categorical Covariate Effects in the Final Population Pharmacokinetic Models
| Parameter | Effect | Change |
|---|---|---|
| Olanzapine | ||
| CL/F | Inducer effect of rifampin (in the presence vs absence of rifampin) in a clinical study 25 | +80% |
| Moderate hepatic impairment vs normal hepatic function in a clinical study 25 | −12% a | |
| Severe renal impairment vs normal renal function in a clinical study 25 | −20% | |
| Smokers vs nonsmokers/not recorded | +30% | |
| Female vs male sex | −14% | |
| Black vs non‐Black | −10% | |
| Bioavailability | Fed vs fasted | −6% |
| Samidorphan | ||
| CL/F | Inducer effect of rifampin (in the presence vs absence of rifampin) in a clinical study 25 | +170% |
| Moderate hepatic impairment vs normal hepatic function in a clinical study 25 | −19% | |
| Severe renal impairment vs normal renal function in a clinical study 25 | −43% | |
| ALAG | Difference for study ALK3831‐A305 b | +10‐fold |
| Nonbilayer tablet vs bilayer tablet | +41% | |
| Ka | Fed vs fasted | −90% |
ALAG, absorption lag time; CL/F, apparent clearance; Ka, first‐order rate of absorption.
a
Effect fixed in the model.
b
Dose time not recorded in ALK3831‐A305, so imputed dose timing used. Consequently, the change in ALAG for this study in comparison to population ALAG was estimated. ALK3831‐A305 had a 4‐week treatment period, and participants received oral study drug once daily. Pharmacokinetic samples were taken predose on the first day of treatment, and subsequently during weeks 2 and 4 of the treatment period.