title: Bioequivalence study with lapatinib powder for oral suspension and the original tablet formulation in cancer patients.
abstract: Lapatinib is approved for use in various therapeutic combinations for treating metastatic breast cancers that over-express HER2. To deliver the approved doses, up to six large tablets need to be ingested with the current 250-mg tablets. For ease of ingestion, a powder for oral suspension was developed. This study was an open-label, randomized, adaptive design, two-period crossover bioequivalence study of the powder for suspension relative to the commercial tablet at steady state following once daily dosing for 7 days in patients with advanced cancer. To minimize the number of cancer patients required for a pivotal bioequivalence study (144 in this case), a four-stage adaptive group sequential design with interim analyses after every 36 subjects was implemented to allow for early termination. Bioequivalence for the oral suspension relative to the commercial tablet was demonstrated in both the first (and only) interim analysis and the final analysis, as the 90% confidence intervals for the treatment comparison ratios for both AUC0-24 and Cmax were contained within the acceptance criteria (0.80, 1.25). Additionally, there was no statistical difference in tlag or tmax , suggesting no difference in the absorption rate between treatments. There were no unexpected safety findings during this study.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Koch
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Ferron-Brady
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Lemmon
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Cartee
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Hedy
authors.initials: H
authors.lastname: Hollyfield
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: D'Amelio
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Piepszak
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Ramona F
authors.initials: RF
authors.lastname: Swaby
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Curran
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Niki
authors.initials: N
authors.lastname: Arya
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004339:Drug Compounding; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D019999:Pharmaceutical Solutions; D011208:Powders; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D014481:United States
chemical_list: D000970:Antineoplastic Agents; D019999:Pharmaceutical Solutions; D011208:Powders; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013607:Tablets; D000077341:Lapatinib
keywords: adaptive group; advanced cancer; bioequivalence; crossover study; lapatinib; sequential design