An open-label, multi-centre drug-drug interaction trial to investigate the effects of tralokinumab on the pharmacokinetics of selected cytochrome P450 (CYP) substrates in adult subjects with moderate-to-severe atopic dermatitis
- Conditions
- atopic dermatitisEczema10040790
- Registration Number
- NL-OMON46290
- Lead Sponsor
- eo Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
* 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.
* 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Ratio of the AUClast at Week 15 (after multiple doses of tralokinumab,<br /><br>AUClast,MD) to that on Day -7 (at baseline, AUClast,Base) for each of the 5<br /><br>substrates<br /><br>- Ratio of the Cmax at Week 15 (Cmax,MD) to that on Day -7 (Cmax,Base) for each<br /><br>of the 5 substrates</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Ratio of the AUClast on Day 8 (after a single dose of tralokinumab,<br /><br>AUClast,SD) to that on Day -7 (AUClast,Base) for each of the 5 substrates<br /><br>- Ratio of the Cmax on Day 8 (Cmax,SD) to that on Day -7 (Cmax,Base) for each<br /><br>of the 5 substrates<br /><br>- Ratio of the AUCinf on Day 8 (AUCinf,SD) to that on Day -7 (AUCinf,Base) for<br /><br>each of the 5 substrates</p><br>