From: Reviewing the role of healthy volunteer studies in drug development
PMID number | Treatment (MOA) | Total studies included | Purpose of population pharmacokinetic model | Key findings | Number of subjects |
---|---|---|---|---|---|
23834452 [74] | Axitinib (VEGFR1, 2, and 3 inhibitor) | 10 (all Phase 1) | Estimate population parameters, evaluate effect of food, formulation, demographics, organ function, metabolic genotype | Volume of distribution increased with body weight, but no impact on drug exposure warranting dose modification | 337 (all healthy) |
28833380 [82] | Selumetinib (MEK inhibitor) | 10 (all Phase 1) | To determine whether the same model is suitable for all formulations and fed conditions and to understand differences in absorption and relative bioavailability with each study | Confirmed previous findings on bioavailability; additional covariates discovered, none requiring dose modification | 346 (all healthy, includes subjects with organ impairment) |
26879594 [75] | Lenvatinib (VEGFR1, 2, and 3, PDGFRβ, RET inhibitor) | 15 (12-Phase 1, 2-Phase 2, 1-Phase 3) | To characterize the PK profile, and identify factors to explain interindividual PK variability in healthy subjects and patients with cancer | No clinically relevant covariates requiring dose adjustment (including demographics, biomarkers, co-administered agents, organ function) | 779 (196 healthy, 583 patients with cancer) |
26898300 [76] | Sonidegib (Smo antagonist) | 5 (4-Phase 1, 1-Phase 2) | To develop a structural PK model in healthy subjects and in patients with cancer, characterize covariate effects, and determine sources of variability | High-fat meals increased bioavailability fivefold, healthy volunteers had threefold higher clearance, no dose adjustments needed based on patient characteristics (patients with cancer) | 436 (85 healthy, 351 patients with cancer) |
29687244 [77] | Cabozantinib (VEGFR2, RET, c-MET inhibitor) | 9 (3-Phase 1, 2-Phase 2, 4-Phase 3) | To analyze the combined PK data from different patient populations and HVs to assess the effect of cancer type, formulation and dose | Small to moderate effect of demographic covariates on apparent clearance (CL/F); Patients with MTC had higher CL/F compared with HVs and other cancer types | 1534 (140 healthy, 1394 patients with cancer) |