Clinical trial NCT00843011: Food and Relative Bioavailability Study
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Depressive Disorder
Keywords: formulation
safety and tolerability
pharmacokinetics
NK1 antagonist
effect of food
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-02-13
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pharmacokinetic:parameters of orvepitant: tlag, tmax, Cmax, AUC(0-t), AUC (0-∞), t1/2.
timeFrame: 72 hours post dose.
measure: Safety and tolerability endpoints will be evaluated by adverse event monitoring,laboratory values, cardiovascular monitoring
timeFrame: 5 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Verona
country: Italy
facility: GSK Investigational Site
state: Veneto
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: