Table 3.

NONMEM parameter estimates for the final population PKPD model

Parameter	Estimate (95% CI)a	RSE	IIV	Shrinkage
CL, mL/hb, c	6.72 (6.43, 7.04)	2.9%	21.2%	20.8%
Vc, Lb, d	2.42 (2.31, 2.53)	2.4%	17.8%	27.0%
Q, mL/hb	12.7 (10.3, 16.6)	20.4%
Vp, Lb	2.06 (1.92, 2.23)	6.4%	16.4%	40.7%
Vmax, µg/h	41.5 (36.2, 47.5)	7.8%	27.0%	53.8%
Km, mg/L	0.966 (0.751, 1.19)	13.7%	26.6%	76.4%
EC50 MAb effect on epiregulin, mg/L	3.42 (3.11, 3.75)	5.9%	19.5%	65.7%
Baseline epiregulin, pg/mL	278 (270, 285)	1.6%	24.9%	6.8%
Kdeg epiregulin, /h	0.0234 (0.0222, 0.0246)	3.1%	26.2%	42.7%
Hill factor effect on epiregulin	0.723 (0.697, 0.748)	2.0%	14.3%	36.1%
Allometric exponent of WT on CLb	1.06 (0.926, 1.21)	9.7%
Allometric exponent of WT on Qb	2.81 (2.04, 3.56)	27.7%
Allometric exponent of WT on Vcb	0.623 (0.510, 0.736)	9.4%
Allometric exponent of WT on Vpb	1.06 (0.827, 1.28)	22.2%
GFR on CLb,c	1.23 (1.11, 1.36)	25.1%
Sex on CLb,c	1.17 (1.10, 1.23)	19.2%
Sex on Vcb,d	1.18 (1.13, 1.23)	16.0%
DPNP on Vcb,d	0.903 (0.857, 0.955)	29.5%
OA on Vcb,d	1.01 (0.952, 1.07)	408.2%
RUV LY3016859, %	13.8 (13.3, 14.3)	3.7%		14.3%
RUV Epiregulin, %	18.1 (17.4, 18.8)	3.6%		14.1%

CL clearance, DPNP diabetic peripheral neuropathic pain, EC₅₀ fepixnebart concentration at 50% effect on epiregulin, GFR body surface area adjusted glomerular filtration rate calculated using the six-variable Modification of Diet in Renal Disease Study equation, IIV interindividual variability, K_deg epiregulin degradation rate in absence of LY3016859, K_m fepixnebart concentration at 50% V_max, OA osteoarthritis, Q inter-compartmental clearance, V_c central volume of distribution, V_max maximum Michaelis–Menten elimination rate, V_p volume of the peripheral compartment, RSE root mean square error, RUV proportional residual unexplained variability (residual error). Shrinkage calculated using the standard deviation.

^a95% CI from sampling importance resampling (SIR)

^bAllometric scaling with weight (for a reference individual of 70 kg) was used for the CL, Q, V_c, and V_p

^c$\text{CL}=e^{\text{log}\left(6.72\right)+0.21\times \frac{\text{log}\left(\frac{\text{GFR}}{88}\right)}{\text{log}\left(119\right)-\text{log}\left(65\right)}+\text{CLSEX}+1.06\times \text{log}\left(\frac{\text{WT}}{70}\right)}$, where WT is body weight and 88 is the median GFR and 65–119 is the 95% percentile range of the GFR data and CLSEX = 0 for male and 0.153 for female patients

^d$V_{\text{c}}=e^{log\left(2.42\right)+\text{VCSEX}+\text{VCSTUDY}+0.623\times \text{log}\left(\frac{\mathit{WT}}{70}\right)}$, where WT is the body weight, VCSEX = 0 for male and 0.162 for female patients, and VCSTUDY = 0, − 0.102, 0.00735 for patients with CLBP, DPNP, and OA patients, respectively