title: A Phase 1, Randomized, Single-Dose Crossover Pharmacokinetic Study to Investigate the Effect of Food Intake on Absorption of Orteronel (TAK-700) in Healthy Male Subjects.
abstract: This study aimed to determine the impact of food on the pharmacokinetics of orteronel, an investigational nonsteroidal, reversible selective inhibitor of 17,20-lyase. In this open-label, randomized crossover study, healthy subjects received single doses of orteronel 400 mg with a low-fat meal, a high-fat meal, and under fasting conditions in a randomized sequence. Plasma concentrations of orteronel and its primary M-I metabolite were determined by ultra-performance liquid chromatography, and pharmacokinetic parameters were evaluated using mixed-effects analysis of variance model. Compared with fasting conditions, the oral bioavailability of orteronel was increased under fed conditions. The least-squares mean ratio for area under the plasma concentration-time curve after a low-fat breakfast was 135% (90% confidence interval [CI], 126%-145%) compared with fasting conditions. Similarly, after a high-fat breakfast, the corresponding value was 142% (90%CI, 132%-152%). No unexpected safety concerns were raised with orteronel 400 mg administered in the fasted state or after either a high-fat or a low-fat meal; mild adverse events were experienced by 36% of the healthy male subjects.
authors.affiliation: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
authors.forename: Ajit
authors.initials: A
authors.lastname: Suri
authors.affiliation: PPD Development, LP, Austin, TX, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Pham
authors.affiliation: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
authors.forename: David B
authors.initials: DB
authors.lastname: MacLean
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004041:Dietary Fats; D005215:Fasting; D018565:Food-Drug Interactions; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004041:Dietary Fats; D007093:Imidazoles; D009281:Naphthalenes; D013254:Steroid 17-alpha-Hydroxylase; C571806:orteronel
keywords: drug bioavailability; food effects; orteronel; pharmacokinetic, metastatic castration-resistant prostate cancer