Atopic Dermatitis
Conditions
Brief 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
Interventions
DRUGTralokinumab
Human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. Presented as a liquid formulation for subcutaneous injection.
DRUGCaffeine
1x 100 mg tablet
DRUGWarfarin
2x 5 mg tablets
DRUGOmeprazole
1x 20 mg capsule
DRUGMetoprolol
1x 100 mg tablet
1 mL of 2 mg/mL oral solution/syrup
Sponsors
LEO Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of the AUC-last at Week 15 (after multiple doses of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates | Day -7 and Week 15 | AUC-last = area under the plasma concentration curve from time 0 to the last quantifiable observation |
| Ratio of the Cmax at Week 15 (after multiple doses of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates | Day -7 and Week 15 | Cmax = maximum observed plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of the AUC-inf on Day 8 (after a single dose of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates | Day -7 and Day 8 | AUC-inf = area under the plasma concentration curve from time 0 to infinity |
| Ratio of the AUC-last on Day 8 (after a single dose of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates | Day -7 and Day 8 | AUC-last = area under the plasma concentration curve from time 0 to the last quantifiable observation |
| Presence of anti-drug antibodies (yes/no) | From Day 1 up to Week 30 | — |
| Number of adverse events | From Day 1 up to Week 30 | — |
| Ratio of the Cmax on Day 8 (after a single dose of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates | Day -7 and Day 8 | Cmax = maximum observed plasma concentration |
Countries
France, Netherlands, United States
Outcome results
None listed