Table 3 Summary of key pharmacokinetic parameters for LYA and LYB.

The pharmacokinetics of LYA and LYB were analyzed with conventional noncompartmental analysis methods to obtain Cmax (maximum drug concentration), Ctrough, and tmax (time of maximum observed drug concentration) at steady state. They were also analyzed with population PK analysis methods based on a one-compartment model with first-order absorption to obtain PK parameters such as CL/F (apparent clearance) and V/F (apparent volume of distribution) and to derive parameters such as t1/2 and AUCss,24hr (area under the concentration versus time profile at steady state over 24 hours). As reference, the IC90 (drug concentration to achieve 90% of the maximum inhibition effect) of the in vitro target engagement assay was 113 ng/ml for LYA, and the IC80 of the in vitro target engagement assay was 864 ng/ml for LYB. Ctrough,ss, predose concentration at steady state.

Parameter based on
noncompartmental
analysis
LYA (n = 39)LYB (n = 42)
EstimateEstimate
Steady-state Cmax
(ng/ml)*
722 (67.0%)7930 (75.5%)
Steady-state Ctrough,ss
(ng/ml)*
436 (77.8%)3080 (68.2%)
Steady-state tmax
(hours)
3.13 (0.85–5.33)3.07 (0.75–4.68)
Parameter based on
population PK
analyses
Population estimatePopulation estimate
CL/F (liters/hour)3.12 (2.66–3.71)7.18 (5.45–8.42)
V/F (liters)39.5 (35.5–50.2)89.3 (34.7–141)
t1/2 (hours)§8.788.62
AUCss,24hr (mg·hour/
liter)║
15.3 (38.7)115 (35.0)

*Reported as geometric mean [geometric %CV (percent coefficient of variation)].

†Reported as median (range).

‡Reported as mean (95% confidence interval).

§Derived using the population estimate of CL/F and V/F based on the following equation: log(2)/(CL/V).

║Reported as geometric mean (%CV), calculated using the post hoc estimate of CL/F of each patient, following the equation dose/(CL/F).