Effect of Multiple Doses of Itraconazole on the Multiple Dose Pharmacokinetics of Lu AE58054 in Healthy Subjects

Interventional, Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of Itraconazole (Inhibitor of CYP3A4/5) on the Multiple Dose Pharmacokinetics of Lu AE58054 in Healthy Subjects

To examine the effect of the strong CYP3A4/5 inhibitor itraconazole (200 mg QD) on the multipledose exposure of Lu AE58054 (30 mg QD) in healthy subjects (CYP2D6 extensive metabolisers).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Lu AE58054 30 mg; Drug: Lu AE58054 30 mg + itraconazole 200 mg; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35042
    • FR801

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects are eligible for inclusion into the study if they meet each of the following criteria:

• Men and women, aged 18 - 45 years.
• Body weight at least 50 kg and Body Mass index 19 - 28 kg/m2.
• Good general health ascertained by a detailed medical history, laboratory tests and physical examination.
• Non-childbearing potential or use of contraception (both sexes).
• Women must not be pregnant or lactating.
• Known CYP2D6 genotype (Extensive metaboliser (n=15) and poor metaboliser (n =5)) .

Other Inclusion and Exclusion Criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lu AE58054 30 mg + itraconazole 200 mg	Drug: Lu AE58054 30 mg; Lu AE58054 encapsulated film-coated tablets, once daily, Day 1-5, orally; Drug: Lu AE58054 30 mg + itraconazole 200 mg; Lu AE58054 encapsulated film-coated tablets, once daily, Day 6-11, orally + itraconazole capsules, once daily, Day 6-11, orally; Drug: Itraconazole; Itraconazole capsules, once daily, Day 12-13, orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the Lu AE58054 plasma concentration-time curve from time zero to 24 hours post-dose (AUC0-24)	Day 5 and Day 11
Maximum observed concentration (Cmax) of Lu AE58054	Day 5 and Day 11

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma pharmacokinetics for Lu AE58054: AUC0-24, Cmax, time at which maximum observed plasma concentration occurred (tmax), apparent oral clearance (CL/F), half life (t½) and apparent volume of distribution Vz/F	Day 5 and Day 11
Plasma pharmacokinetics for relevant metabolites: AUC0-24, Cmax, tmax, t½ and metabolic ratio (MR)	Day 5 and Day 11
Plasma pharmacokinetic parameters for itraconazole: CTrough	Day 6 to Day 13
Adverse events	Up to Day 18, including a safety follow-up
Columbia Suicide Severity Rating Scale (C-SSRS) categorization based on Columbia Classification Algorithm of Suicide Assessment (C-CASA) definitions	Up to Day 18, including a safety follow-up

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: April 23, 2014
• First Submitted That Met QC Criteria: April 23, 2014
• First Posted (Estimate): April 24, 2014

Study Record Updates

• Last Update Posted (Estimate): June 19, 2014
• Last Update Submitted That Met QC Criteria: June 18, 2014
• Last Verified: June 1, 2014

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; Hydroxyitraconazole
• Other Study ID Numbers: 15820A; 2013-003597-27 (EudraCT Number)