food and relative bioavailability study

Conditions: Depressive Disorder

Summary: this study is an open-label, randomised, single dose study to determine the pharmacokinetics, safety and tolerability of 2 different formulations of orvepitant 60 mg and the effect of food in 15 healthy volunteers.

orvepitant is a highly potent and selective neurokinin-1 (nk1) receptor antagonist currently in development for the treatment of depression and anxiety. this study is an open-label, randomised, single dose study to determine the pharmacokinetics, safety and tolerability of 2 different formulations of orvepitant 60 mg and the effect of food in 15 healthy volunteers. according to a cross over design, in three different occasions, each subject will receive the "old" formulation of orvepitant in fasted condition and the "new" formulation in fasted condition and after a fda high-fat breakfast. subjects will be screened within 21 days of first treatment. on each dosing occasion, subjects will be admitted to the clinic on day-1 and will remain until day 2; they will be also asked to return to the site 48 and 72 hours after each dosing for the pk blood sample collection. the wash-out period between each dosing occasion will be at least 5 days and subjects will be asked to return to the site 7-14 days after the administration of the last dose of orvepitant for a follow-up visit.

Eligibility criteria:
inclusion criteria: * healthy male or female between 18 and 65 years of age inclusive. * a female subject is eligible to participate if she is of either non-childbearing potential or child-bearing potential and agrees to use one of the contraception methods * no co-morbid psychiatric disorders as defined using the mini international neuropsychiatric interview (m.i.n.i) scale. * a 12-lead ecg at screening showed no abnormalities that in the opinion of the principal investigator will compromise safety in this study. -- body weight ≥ 50 kg and bmi within the range 19.0 - 29.9 kg/m2 (inclusive). * capable of giving written informed consent exclusion criteria: * as a result of any of the medical interview, physical examination or screening investigations the physician responsible considers the subject unfit for the study. * the subject has a history of a drug or other allergy which in the opinion of the physician responsible contraindicates the participation in the study. * subjects with an unstable medical disorder or a disorder that would likely interfere with the action, absorption, distribution, metabolism or excretion of orvepitant, may pose a safety concern, or interfere with accurate assessment of safety. * the subject has a current or recent (within six months) documented gastrointestinal disease; a history of malabsorption, oesophageal reflux, or irritable bowel syndrome; frequent (more than once a week) occurrence of heartburn, or any surgical intervention (e.g. cholecystectomy) which would be expected to influence the absorption of drugs. * history of psychiatric illness * any history of a clinically significant abnormality of the neurological system (including dementia and other cognitive disorders or significant head injury) or any history of seizure (excluding febrile seizure). * subject is consuming alcool or tobacco * subject is positive to hepatitis b, c or hiv

Keywords: formulation safety and tolerability pharmacokinetics nk1 antagonist effect of food