Drug-drug Interaction Trial With Tralokinumab in Moderate to Severe Atopic Dermatitis - ECZTRA 4
- Conditions
- Atopic Dermatitis
- Interventions
- Registration Number
- NCT03556592
- Lead Sponsor
- LEO Pharma
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
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Age 18 and above.
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Diagnosis of AD as defined by the Hanifin and Rajka 1980 criteria for AD.
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History of AD for ≥1 year.
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Subjects who have a recent history of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable.
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AD involvement of ≥10% body surface area at screening and baseline.
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Stable dose of emollient twice daily (or more, as needed) for at least 14 days before baseline.
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Willingness to abstain from consumption of any 1 or more of the following items in the periods specified:
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±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.
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±48 hours within each cocktail dosing visit: caffeinated beverages and foods/drugs that contain caffeine.
-
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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.
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Subjects who are poor metabolisers of CYP2C9, CYP2C19, or CYP2D6, based on genotyping.
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Any contraindication to 1 or more of the following drugs, according to the applicable labelling: caffeine, warfarin, omeprazole, metoprolol, or midazolam.
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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.
-
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Nausea or diarrhoea 1 week prior to Day -7.
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Active dermatologic conditions that may confound the diagnosis of AD.
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Use of tanning beds or phototherapy within 5 weeks prior to Day -7.
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Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 3 weeks prior to Day -7.
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Treatment with topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase 4 inhibitors within 1 week prior to Day -7.
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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.
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Active skin infection within 1 week prior to Day -7.
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Clinically significant infection within 4 weeks prior to Day -7.
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A helminth parasitic infection within 6 months prior to the date informed consent is obtained.
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Tuberculosis requiring treatment within 12 months prior to screening.
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Known primary immunodeficiency disorder.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description All subjects Midazolam Hydrochloride Tralokinumab - investigational medicinal product: Week 0: subcutaneous (SC) injection of tralokinumab loading dose. Week 2 to Week 14: SC injection of tralokinumab maintenance dose. CYP substrates - non-investigational medicinal products: Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg. All subjects Warfarin Tralokinumab - investigational medicinal product: Week 0: subcutaneous (SC) injection of tralokinumab loading dose. Week 2 to Week 14: SC injection of tralokinumab maintenance dose. CYP substrates - non-investigational medicinal products: Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg. All subjects Omeprazole Tralokinumab - investigational medicinal product: Week 0: subcutaneous (SC) injection of tralokinumab loading dose. Week 2 to Week 14: SC injection of tralokinumab maintenance dose. CYP substrates - non-investigational medicinal products: Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg. All subjects Tralokinumab Tralokinumab - investigational medicinal product: Week 0: subcutaneous (SC) injection of tralokinumab loading dose. Week 2 to Week 14: SC injection of tralokinumab maintenance dose. CYP substrates - non-investigational medicinal products: Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg. All subjects Caffeine Tralokinumab - investigational medicinal product: Week 0: subcutaneous (SC) injection of tralokinumab loading dose. Week 2 to Week 14: SC injection of tralokinumab maintenance dose. CYP substrates - non-investigational medicinal products: Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg. All subjects Metoprolol Tralokinumab - investigational medicinal product: Week 0: subcutaneous (SC) injection of tralokinumab loading dose. Week 2 to Week 14: SC injection of tralokinumab maintenance dose. CYP substrates - non-investigational medicinal products: Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg.
- Primary Outcome Measures
Name Time Method 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
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
- Secondary Outcome Measures
Name Time Method 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
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
Trial Locations
- Locations (1)
LEO Pharma Investigational Site
🇳🇱Leiden, Netherlands