Clinical trial NCT03556592: Drug-drug Interaction Trial With Tralokinumab in Moderate to Severe Atopic Dermatitis - ECZTRA 4
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atopic Dermatitis
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2018-06-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Day -7 and Week 15
measure: 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
timeFrame: Day -7 and Week 15
Secondary outcomes:
measure: 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
timeFrame: Day -7 and Day 8
measure: 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
timeFrame: Day -7 and Day 8
measure: 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
timeFrame: Day -7 and Day 8
measure: Number of adverse events
timeFrame: From Day 1 up to Week 30
measure: Presence of anti-drug antibodies (yes/no)
timeFrame: From Day 1 up to Week 30
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: LEO Pharma Investigational Site
state: Arkansas
city: Rogers
country: United States
facility: LEO Pharma Investigational Site
state: Arkansas
city: San Diego
country: United States
facility: LEO Pharma Investigational Site
state: California
city: Doral
country: United States
facility: LEO Pharma Investigational Site
state: Florida
city: Miami
country: United States
facility: LEO Pharma Investigational Site
state: Florida
city: Miami
country: United States
facility: LEO Pharma Investigational Site
state: Florida
city: Quincy
country: United States
facility: LEO Pharma Investigational Site
state: Massachusetts
city: Spartanburg
country: United States
facility: LEO Pharma Investigational Site
state: South Carolina
city: Norfolk
country: United States
facility: LEO Pharma Investigational Site
state: Virginia
city: Nice
country: France
facility: LEO Pharma Investigational Site
city: Paris
country: France
facility: LEO Pharma Investigational Site
city: Leiden
country: Netherlands
facility: LEO Pharma Investigational Site
Study officials:
affiliation: LEO Pharma
name: Medical expert
role: STUDY_DIRECTOR
References: