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

• Published in: Clinical pharmacology in drug development 2016-05, Vol.5 (3), p.188-195
• Main Authors: Suri, Ajit, Pham, Theresa, MacLean, David B.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adolescent; Adult; Biological Availability; Chromatography, High Pressure Liquid; Confidence intervals; Cross-Over Studies; Cytochrome P-450 Enzyme Inhibitors - administration & dosage; Cytochrome P-450 Enzyme Inhibitors - adverse effects; Cytochrome P-450 Enzyme Inhibitors - pharmacokinetics; Dietary Fats; drug bioavailability; Fasting; food effects; Food-Drug Interactions; Hogs; Humans; Imidazoles - administration & dosage; Imidazoles - adverse effects; Imidazoles - pharmacokinetics; Least-Squares Analysis; Male; metastatic castration-resistant prostate cancer; Middle Aged; Naphthalenes - administration & dosage; Naphthalenes - adverse effects; Naphthalenes - pharmacokinetics; orteronel; pharmacokinetic; pharmacokinetic, metastatic castration‐resistant prostate cancer; Steroid 17-alpha-Hydroxylase - antagonists & inhibitors; Young Adult
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.233

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.