17208A Itraconazole on the PK, Safety and Tolerability of Lu AF35700
Research type
Research Study
Full title
Interventional, open-label, one-sequence crossover study evaluating the effect of multiple doses of itraconazole (inhibitor of CYP3A4/5) on the pharmacokinetics, safety and tolerability of Lu AF35700 in healthy young men and women
IRAS ID
220217
Contact name
Ashley Brooks
Contact email
Sponsor organisation
H. Lundbeck A/S
Eudract number
2016-003302-14
Duration of Study in the UK
0 years, 5 months, 11 days
Research summary
Lu AF35700 is a new medicine that is being developed as a potential antipsychotic therapy in patients with treatment-resistant schizophrenia - a condition characterised by disturbances in thinking, perception and emotion. Lu AF35700 acts on several receptors (proteins) in the body (known as serotonergic, dopaminergic and alpha-adrenergic receptors).
Lu AF35700 is broken down through various metabolic pathways - CYP2D6, CYP3A4/5 and CYP2C19.
Itraconazole is an antifungal medication currently on the market for the treatment of fungal infections. It is also a strong inhibitor of the CYP3A4/5 pathway. It is commonly given in these types of studies to assess the involvement of the CYP3A4/5 pathway on the elimination of study drugs.
This study will evaluate the effect of multiple doses of itraconazole on the study drug Lu AF35700 in healthy males and females. The study will be divided into 2 parts - Part A and Part B.
Part A will consist of 2 cohorts of 10 subjects (A1 and A2) - they will be CYP2D6 extensive metabolisers with known CYP2C19 genotype. Part B will consist of 8 subjects - they will be CYP2D6 poor metabolisers with known CYP2C19 genotype.
Approximately 8% of the Caucasian population are CYP2D6 poor metabolisers - this means that they may break down certain compounds more slowly compared to extensive metabolisers. CYP2D6 extensive metabolisers and poor metabolisers will be identified by genotyping (blood tests). The main study analysis will be performed in CYP2D6 extensive metabolisers, whilst a group of poor metabolisers will be included to explore the extent of the CYP3A4/5 metabolic inhibition (by itraconazole) in subjects who cannot break down the study drug by using the CYP2D6 metabolic pathway. Only 1-5% of the Caucasian population are CYP2C19 poor metabolisers. For the CYP2D6 poor metabolisers it is important to know their CYP2C19 genotype in order to potentially exclude subjects that are both CYP2D6 and CYP2C19 poor metabolisers - data from Part A of the study will guide dose level and inclusion of CYP2C19 metaboliser status in Part B.
Parts A and B of the study will each consist of 3 treatment periods.
In Treatment period 1 (Days 1-28), each subject will on Day 1 receive a single dose of Lu AF35700 (10mg in Part A and 5 or 10mg in Part B) followed by a washout on Days 2-28. In this treatment period, subjects will be in-clinic for 5 days and then come back on Day 28.
In Treatment period 2 (Days 29-31), each subject will receive a once-daily dose of 200mg itraconazole. In this treatment period, subjects will be confined to the clinic.
In Treatment period 3 (Days 32-74), each subject will on Day 32 be given a single dose of Lu AF35700 (10mg in Part A, and 5mg or 10mg in Part B, depending on the results from Part A, cohort A1) as well as a 300mg dose of itraconazole. On Days 33-42 a once-daily dose of 200mg itraconazole will be given. In this treatment period, subjects will be confined to the clinic for 11 days.
REC name
North East - York Research Ethics Committee
REC reference
17/NE/0002
Date of REC Opinion
3 Mar 2017
REC opinion
Further Information Favourable Opinion