A Pharmacokinetic Study of the Effect of Itraconazole Exposure to Orvepitant in Healthy Volunteers

Study Overview
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Brief Summary
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A Phase 1 study to assess the effect of itraconazole, a strong inhibitor of CYP3A and P-glycoprotein, on the pharmacokinetics (PK) of orvepitant in healthy male volunteers. Subjects will receive two single doses of 20mg orvepitant, once alone and once in combination with repeat doses of itraconazole. All subjects will follow the same sequence - orvepitant alone followed by orvepitant in combination with itraconazole.

Official Title
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A Phase 1, Open-Label, Single-Sequence Crossover Study in Healthy Male Participants to Determine the Effect of an Inhibitor of Cytochrome P450 3A and P Glycoprotein on Exposure to Orvepitant

Conditions
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Pharmacokinetic Study in Healthy Male Volunteers

Intervention / Treatment
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* Drug: Orvepitant
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: male volunteers judged to be in good health, based on the results of medical history, physical examination, vital signs, 12 lead ECG, and clinical laboratory findings body weight greater than 50 kg and body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive) Key Exclusion Criteria: clinically significant findings on physical examination relevant medical history history of or considered at high risk of seizures (except febrile fits in childhood), including history of significant head injury positive serology for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV) or human immunodeficiency virus (HIV) serum biochemistry and full blood count considered by the Investigator to be of clinical significance systolic blood pressure <100 or >140 mmHg or diastolic BP <50 or ˃90 mmHg, measured prior to the first dose of orvepitant abnormal 12 lead electrocardiogram (ECG) has donated one or more units (approximately 450 mL) of blood or acute loss of an equivalent amount of blood within 90 days prior to study intervention administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orvepitant<br>Orvepitant single 20mg dose | Drug: Orvepitant<br>* Single oral dose<br>|
| Experimental: Orvepitant and itraconazole<br>Orvepitant single 20mg dose in combination with repeat dose itraconazole | Drug: Orvepitant<br>* Single oral dose<br>Drug: Itraconazole<br>* Once daily dosing for 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exposure to orvepitant | Area Under Curve (AUC) | 0 to 168 hours post dose |