A Study of the Effect of Multiple Doses of Itraconazole and Fluoxetine on the Pharmacokinetics of a Single Dose of RO5285119 in Healthy Subjects

A Single-Center, Open-Label, One-Sequence, 2-Period, Within-Subject Study in 2 Cohorts to Investigate the Effect of Multiple Doses of Itraconazole (Cohort 1) and Fluoxetine (Cohort 2) on the Pharmacokinetics of a Single Dose of RO5285119 in Healthy Subjects

This single-center, open-label, one-sequence, 2-period, within-subject study in 2 cohorts will evaluate the effects of multiple doses of itraconazole and fluoxetine on the pharmacokinetics of a single dose of RO5285119 in healthy volunteers. In Cohort 1, subjects will receive a single dose of RO5285119 on Day 1 (Period 1) and, after a wash-out period of 14 days, itraconazole on Days 1-8 of Period 2 with coadministration of RO5285119 on Day 4. In Cohort 2, subjects will receive a single dose of RO5285119 on Day 1 (Period 1) and, after a wash-out period of 14 days, fluoxetine on Days 1-12 of Period 2 with coadministration of RO5285119 on Day 6.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: RO5285119; Drug: itraconazole; Drug: fluoxetine

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands, 9471 GP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female subjects, 18 to 55 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, and a complete physical examination
• Body mass index (BMI) between 18 to 30 kg/m2 inclusive
• Women must be postmenopausal (for at least 12 months of amenorrhea confirmed by FSH, or for at least 24 months if on hormone replacement therapy) or surgically sterile (absence of ovaries and/or uterus)
• For men with a female partner of child-bearing potential: agreement to use a barrier method of contraception during the treatment period and for at least 3 months after the last dose of study drug

Exclusion Criteria:

• Suspicion of regular consumption of drug of abuse, or history of drug or alcohol abuse
• Positive for hepatitis B, hepatitis C , or HIV infection
• Participation in an investigational drug or device study within 90 days prior to first dosing
• Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
• Hypersensitivity to itraconazole, to any of the other ingredients, or to any other triazole antifungal, or any other known contraindications to itraconazole as stated in the SmPC
• Hypersensitivity to fluoxetine or to any of the other ingredients, or any other known contraindications to fluoxetine as stated in the SmPC

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Itraconazole DDI)	Drug: RO5285119; Single dose, alone and after repeated administration of itraconazole or fluoxetine; Drug: itraconazole; Multiple doses
Experimental: Cohort 2 (Fluoxetine DDI)	Drug: RO5285119; Single dose, alone and after repeated administration of itraconazole or fluoxetine; Drug: fluoxetine; Multiple doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of multiple doses of itraconazole and fluoxetine on the pharmacokinetics of a single dose of RO5285119 in healthy volunteers: Maximum concentration (Cmax) / Area under the concentration-time curve (AUC)	up to 5 and 7 days post-dose for cohort 1 and cohort 2, respectively

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of a single dose of RO5285119 administered in combination with itraconazole (cohort 1) and fluoxetine (cohort 2): Incidence of adverse events	up to 6 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimate): October 23, 2013

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Fluoxetine
• Other Study ID Numbers: BP28977; 2013-003232-76 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No