Food and Relative Bioavailability Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Open-label, Randomized, Single-dose, 3-way Crossover Study to Investigate the Pharmacokinetics, Safety and Tolerability of 2 Different Formulations of Orvepitant and the Effect of Food in Healthy Volunteers.

Conditions
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Depressive Disorder

Intervention / Treatment
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* Drug: Orvepitant


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Orvepitant 60 mg | Drug: Orvepitant<br>* Orvepitant 60 mg, single dose. 2 different formulation. Formulation 2 is administered with and without food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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formulation, safety and tolerability, pharmacokinetics, NK1 antagonist, effect of food