Drug-drug Interaction Trial With Tralokinumab in Moderate to Severe Atopic Dermatitis - ECZTRA 4

• Status: Completed
• Trial end date: 2020-06-20
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this trial is to investigate if tralokinumab changes the metabolism of selected CYP substrates in adults with moderate-to-severe AD after:

• 14 weeks of treatment with tralokinumab

• a single dose of tralokinumab

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: LEO Pharma
• Treatments: Caffeine; Metoprolol; Midazolam; Omeprazole; Warfarin

Criteria

Inclusion Criteria:

• Age 18 and above.

• Diagnosis of AD as defined by the Hanifin and Rajka 1980 criteria for AD.

• History of AD for ≥1 year.

• Subjects who have a recent history of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable.

• AD involvement of ≥10% body surface area at screening and baseline.

• Stable dose of emollient twice daily (or more, as needed) for at least 14 days before baseline.

• Willingness to abstain from consumption of any 1 or more of the following items in the periods specified:

• ±7 days within each cocktail dosing visit: foods/beverages that affect the CYP system:

• Grapefruit or grapefruit juice, Seville oranges or orange juice, starfruit, pomegranate and cranberry juices, red wine, red grape extract.

• Cruciferous vegetables (for example broccoli).

• Chargrilled meat.

• ±48 hours within each cocktail dosing visit: caffeinated beverages and foods/drugs that contain caffeine.

Exclusion Criteria:

• Administration, within 14 days or 5 half-lives (whichever is longer) prior to Day -7, of any medication that is a known inducer or inhibitor of 1 or more of the following CYP enzymes: CYP3A, CYP2C19, CYP2C9, CYD2D6, and CYP1A2.

• Subjects who are poor metabolisers of CYP2C9, CYP2C19, or CYP2D6, based on genotyping.

• Any contraindication to 1 or more of the following drugs, according to the applicable labelling: caffeine, warfarin, omeprazole, metoprolol, or midazolam.

• Consumption of any 1 or more of the following items in the periods specified:

• ±7 days within each cocktail dosing visit: foods/beverages that affect the CYP system:

• Grapefruit or grapefruit juice, Seville oranges or orange juice, starfruit, pomegranate and cranberry juices, red wine, red grape extract.

• Cruciferous vegetables (for example broccoli).

• Chargrilled meat.

• ±48 hours within each cocktail dosing visit: caffeinated beverages and foods/drugs that contain caffeine.

• Nausea or diarrhoea 1 week prior to Day -7.

• Active dermatologic conditions that may confound the diagnosis of AD.

• Use of tanning beds or phototherapy within 5 weeks prior to Day -7.

• Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 3 weeks prior to Day -7.

• Treatment with topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase 4 inhibitors within 1 week prior to Day -7.

• Receipt of any marketed biological therapy or investigational biologic agent (including immunoglobulin, anti-IgE, or dupilumab):

• Any cell-depleting agents, including but not limited to rituximab: within 6 months prior to Day -7, or until lymphocyte count returns to normal, whichever is longer.

• Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to Day -7.

• Active skin infection within 1 week prior to Day -7.

• Clinically significant infection within 4 weeks prior to Day -7.

• A helminth parasitic infection within 6 months prior to the date informed consent is obtained.

• Tuberculosis requiring treatment within 12 months prior to screening.

• Known primary immunodeficiency disorder.