atopic dermatitis Eczema
Conditions
Interventions
Tralokinumab
CYP cocktail:
- Caffeine
- Warfarin
- Omeprazole
- Metoprolol
- Midazolam
Atopic dermatitis
Drug-drug interaction
Pharmacokinetics
Tralokinumab
Sponsors
Leo Pharma
Eligibility
Age
18 Years to 64 Years
Inclusion 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: o ±7 days within each cocktail dosing visit (that is, between the Day -14 and Day 15 visits and between the Week 14 and Week 16 visits): 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, including but not limited to broccoli, cabbage, cauliflower, kale, Brussels sprout, radish, turnip, horseradish. - Chargrilled meat. o ±48 hours within each cocktail dosing visit: caffeinated beverages, foods/drugs that contain caffeine, including coffee, tea (black and green), coca cola, energy drinks, and chocolate.
Exclusion criteria
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: o From Day -14 (±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, including but not limited to broccoli, cabbage, cauliflower, kale, Brussels sprout, radish, turnip, horseradish. - Chargrilled meat. o From Day -9 (±48 hours within each cocktail dosing visit): caffeinated beverages, foods/drugs that contain caffeine, including coffee, tea (black and green), coca cola, energy drinks, and chocolate. * 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 (that is, immunoglobulin or anti-immunoglobulin E) including dupilumab or investigational biologic agents: o Any cell-depleting agents, including but not limited to rituximab: within 6 months prior to baseline (Day -7), or until lymphocyte count returns to normal, whichever is longer. o Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to baseline (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 the 12 months prior to screening. * Known primary immunodeficiency disorder.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Ratio of the AUClast at Week 15 (after multiple doses of tralokinumab, AUClast,MD) to that on Day -7 (at baseline, AUClast,Base) for each of the 5 substrates - Ratio of the Cmax at Week 15 (Cmax,MD) to that on Day -7 (Cmax,Base) for each of the 5 substrates | — |
Secondary
| Measure | Time frame |
|---|---|
| - Ratio of the AUClast on Day 8 (after a single dose of tralokinumab, AUClast,SD) to that on Day -7 (AUClast,Base) for each of the 5 substrates - Ratio of the Cmax on Day 8 (Cmax,SD) to that on Day -7 (Cmax,Base) for each of the 5 substrates - Ratio of the AUCinf on Day 8 (AUCinf,SD) to that on Day -7 (AUCinf,Base) for each of the 5 substrates | — |
Countries
France, Netherlands, United States of America
Outcome results
None listed