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Drug-drug Interaction Trial With Tralokinumab in Moderate to Severe Atopic Dermatitis - ECZTRA 4 (ECZema TRAlokinumab Trial no. 4)

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ClinicalTrials.gov Identifier: NCT03556592
Recruitment Status : Not yet recruiting
First Posted : June 14, 2018
Last Update Posted : June 14, 2018
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Atopic Dermatitis Drug: Tralokinumab Drug: Caffeine Drug: Warfarin Drug: Omeprazole Drug: Metoprolol Drug: Midazolam Hydrochloride Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multi Centre Drug-drug Interaction Trial to Investigate the Effects of Tralokinumab on the Pharmacokinetics of Selected Cytochrome P450 Substrates in Adult Subjects With Moderate-to-severe Atopic Dermatitis
Estimated Study Start Date : June 25, 2018
Estimated Primary Completion Date : June 25, 2019
Estimated Study Completion Date : October 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: All subjects

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.

Drug: Tralokinumab
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.

Drug: Caffeine
1x 100 mg tablet

Drug: Warfarin
2x 5 mg tablets

Drug: Omeprazole
1x 20 mg capsule

Drug: Metoprolol
1x 100 mg tablet

Drug: Midazolam Hydrochloride
1 mL of 2 mg/mL oral solution/syrup




Primary Outcome Measures :
  1. 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 [ Time Frame: Day -7 and Week 15 ]
    AUC-last = area under the plasma concentration curve from time 0 to the last quantifiable observation

  2. 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 [ Time Frame: Day -7 and Week 15 ]
    Cmax = maximum observed plasma concentration


Secondary Outcome Measures :
  1. 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 [ Time Frame: Day -7 and Day 8 ]
    AUC-last = area under the plasma concentration curve from time 0 to the last quantifiable observation

  2. 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 [ Time Frame: Day -7 and Day 8 ]
    Cmax = maximum observed plasma concentration

  3. 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 [ Time Frame: Day -7 and Day 8 ]
    AUC-inf = area under the plasma concentration curve from time 0 to infinity

  4. Number of adverse events [ Time Frame: From Day 1 up to Week 30 ]
  5. Presence of anti-drug antibodies (yes/no) [ Time Frame: From Day 1 up to Week 30 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    • ±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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03556592


Contacts
Contact: LEO Pharma A/S (+1) 877-557-1168 disclosure@leo-pharma.com

Sponsors and Collaborators
LEO Pharma
Investigators
Study Director: Medical expert LEO Pharma

Responsible Party: LEO Pharma
ClinicalTrials.gov Identifier: NCT03556592     History of Changes
Other Study ID Numbers: LP0162-1342
2018-000534-35 ( EudraCT Number )
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Omeprazole
Dermatitis
Dermatitis, Atopic
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Midazolam
Caffeine
Metoprolol
Warfarin
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticoagulants