Drug-drug Interaction Trial With Tralokinumab in Moderate to Severe Atopic Dermatitis - ECZTRA 4

LEO Pharma

Status and phase: Completed; Phase 1

Conditions: Atopic Dermatitis

Treatments: Drug: Caffeine; Drug: Tralokinumab; Drug: Warfarin; Drug: Metoprolol; Drug: Omeprazole; Drug: Midazolam Hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT03556592

2018-000534-35 (EudraCT Number)

LP0162-1342

Details and patient eligibility

About

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

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

All subjects

Experimental group

Description:

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.

Treatment:

Drug: Midazolam Hydrochloride

Drug: Omeprazole

Drug: Metoprolol

Drug: Warfarin

Drug: Tralokinumab

Drug: Caffeine