title: A randomized, three-treatment, three-period, six-sequence-crossover, single-center, bioequivalence study to evaluate the impact of different 10-mg crystalline forms on the pharmacokinetics of lenvatinib in healthy volunteers.
abstract: OBJECTIVE
  This study assessed the impact of varying lenvatinib crystalline forms in 10-mg lenvatinib capsules on drug bioavailability in healthy volunteers.
  
  
  METHODS
  Lenvatinib 10-mg capsules (low C and high C forms).
  
  
  METHODS
  This randomized, three-period- crossover study compared the pharmacokinetics and safety of two crystalline forms of capsules (low C-form, <4% crystalline; high C-form, 38% crystalline) to a standard (ref Cform, 15% crystalline).
  
  
  RESULTS
  59 subjects were evaluable for pharmacokinetics. Test/reference ratios of the geometric least squares means (LSM) and 90% confidence intervals (CI) for AUC0-t (t up to 120 hours), AUC0-∞, and Cmax for low C-form vs. ref C-form were 101 (94.8, 107), 101 (95.3, 107), and 98.7 (88.6, 110), respectively; and for high C-form vs. ref C-form were 96.0 (92.1, 100), 96.5 (92.5, 101), and 90.6 (83.5, 98.4), respectively. The incidence of treatment-emergent adverse events (TEAE) and treatment-related adverse events (TRAE) were comparable between all formulations (TEAE range 20-24%; TRAE range 15-19%). One serious TRAE (spontaneous abortion) occurred in the low C-form group.
  
  
  CONCLUSIONS
  For both comparisons, the 90% CIs of the test/reference ratios were within the regulatory acceptance range (80-125%), suggesting that both test formulations (low Cform and high C-form) were bioequivalent to the reference formulation for Cmax, AUC0-t, and AUC0-∞.
authors.forename: Lucy
authors.initials: L
authors.lastname: Lee
authors.forename: Pina
authors.initials: P
authors.lastname: D'Angelo
authors.forename: David
authors.initials: D
authors.lastname: Verbel
authors.forename: Gresel
authors.initials: G
authors.lastname: Martinez
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Aluri
authors.forename: Darin
authors.initials: D
authors.lastname: Brimhall
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000493:pharmacokinetics*; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics*; D011804:Quinolines / Q000009:adverse effects / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C531958:lenvatinib