TABLE 1.

Population PK parameters and bootstrap CIs for the final lecanemab covariate model

Parameter (units)	NONMEM		Bootstrap
	Estimate	%RSE	Median (95% CI)
PK parameters
CL (L/h)	0.0181	2.55	0.0181 (0.0175–0.0188)
V 1 (L)	3.22	1.18	3.22 (3.15–3.28)
Q (L/h)	0.0349	8.02	0.0349 (0.0294–0.0396)
V 2 (L)	2.19	7.21	2.20 (2.00–2.40)
F for process B	0.998	4.07	0.999 (0.950–1.06)
Covariate effects
Weight ~ CL (exponent)	0.403	9.73	0.393 (0.217–0.495)
Albumin ~ CL (exponent)	−0.243	17.2	−0.237 (−0.405 to −0.0771)
Females ~ CL (ratio)	0.792	3.43	0.790 (0.735–0.825)
ADA positive ~ CL (ratio to ADA negative)	1.09	0.586	1.09 (1.05–1.12)
Weight ~ V 1 (exponent)	0.606	7.52	0.603 (0.548–0.663)
Females ~ V 1 (ratio)	0.893	1.75	0.893 (0.870–0.919)
Japanese race ~ V 2 (ratio)	0.455	24.4	0.450 (0.338–0.583)
Interindividual variability (CV%)
CL	38.9	6.69	38.9 (36.7–40.4)
V 1	14.0	8.38	14.0 (12.7–15.1)
V 2	99.5	7.91	99.8 (84.4–109)
F	34.2	17.7	34.1 (28.7–37.4)
Residual variability (CV%)
Proportional: study 101	14.0	3.49	14.0 (12.6–15.1)
Proportional: study 104	19.7	4.66	19.6 (16.9–22.1)
Proportional: study 201	30.3	0.803	30.2 (28.7–31.2)

Abbreviations: %RSE, percent relative standard error of the estimate = SE/parameter estimate × 100; ADA, anti‐drug antibody; CI, confidence interval; CL, clearance; CV%, square root of variance × 100; F, relative bioavailability; PK, pharmacokinetic; Q, intercompartment clearance; V ₁, central volume of distribution; V ₂, peripheral volume of distribution.

$\mathrm{CL}=0.0181\bullet {\left(\frac{\mathrm{BW}}{73.7}\right)}^{0.403}\bullet {\left(\frac{\mathrm{ALB}}{42.9}\right)}^{-0.243}\bullet {0.792}^{\mathrm{SEX}}\bullet {1.09}^{\mathrm{ADA}}$.

$\mathrm{V}1=3.22\bullet {\left(\frac{\mathrm{BW}}{73.7}\right)}^{0.606}\bullet {0.893}^{\mathrm{SEX}}$.

$\mathrm{V}2=2.19\bullet {0.455}^{\mathrm{JPN}}$.

$F=1\bullet {0.998}^{\text{FORM}}$.

ADA, 0 (ADA negative) or 1 (positive); ALB, albumin; BW, body weight; SEX, 0 (male) or 1 (female); JPN, 0 (non‐Japanese) or 1 (Japanese); FORM, 0 (Process A) or 1 (Process B).

Eta shrinkage (%): ETA_CL, 9.96%; ETA_V ₁, 30.5%, ETA_V ₂, 31.7%, ETA_F1, 63.2%.