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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Lu AE58054 30 mg
* Drug: Lu AE58054 30 mg + itraconazole 200 mg
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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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.

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

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |