drug-drug interaction trial with tralokinumab in moderate to severe atopic dermatitis - ecztra 4

Conditions: Atopic Dermatitis

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


Eligibility 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.