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

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

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetic Study in Healthy Male Volunteers
• Intervention / Treatment: Drug: Orvepitant; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Parexel Epcu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Nerre Therapeutics Ltd.
• Investigators: Principal Investigator: Principal Investigator, Parexel Epcu

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2018
• Primary Completion (Actual): August 9, 2018
• Study Completion (Actual): August 9, 2018

Study Registration Dates

• First Submitted: May 11, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): May 24, 2018

Study Record Updates

• Last Update Posted (Actual): October 11, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: ORV-1-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No