Depressive Disorder
Conditions
Keywords
formulation, safety and tolerability, pharmacokinetics, NK1 antagonist, effect of food
Brief 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.
Detailed description
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.
Interventions
DRUGOrvepitant
Orvepitant 60 mg, single dose. 2 different formulation. Formulation 2 is administered with and without food.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic:parameters of orvepitant: tlag, tmax, Cmax, AUC(0-t), AUC (0-∞), t1/2. | 72 hours post dose. |
| Safety and tolerability endpoints will be evaluated by adverse event monitoring,laboratory values, cardiovascular monitoring | 5 weeks. |
Countries
Italy
Outcome results
None listed