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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03556592
• Other study ID #: LP0162-1342
• Secondary ID: 2018-000534-35
• Status: Completed
• Phase: Phase 1
• Start date: August 13, 2018
• Est. completion date: June 20, 2020

Study information

• Verified date: October 2020
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 20, 2020
• Est. primary completion date: March 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

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.
• Caffeine
1x 100 mg tablet
• Warfarin
2x 5 mg tablets
• Omeprazole
1x 20 mg capsule
• Metoprolol
1x 100 mg tablet
• Midazolam Hydrochloride
1 mL of 2 mg/mL oral solution/syrup

Locations

Country	Name	City	State
France	LEO Pharma Investigational Site	Nice
France	LEO Pharma Investigational Site	Paris
Netherlands	LEO Pharma Investigational Site	Leiden
United States	LEO Pharma Investigational Site	Doral	Florida
United States	LEO Pharma Investigational Site	Little Rock	Arkansas
United States	LEO Pharma Investigational Site	Miami	Florida
United States	LEO Pharma Investigational Site	Miami	Florida
United States	LEO Pharma Investigational Site	Norfolk	Virginia
United States	LEO Pharma Investigational Site	Quincy	Massachusetts
United States	LEO Pharma Investigational Site	Rogers	Arkansas
United States	LEO Pharma Investigational Site	San Diego	California
United States	LEO Pharma Investigational Site	Spartanburg	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Countries where clinical trial is conducted

United States,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	AUC-last = area under the plasma concentration curve from time 0 to the last quantifiable observation	Day -7 and Week 15
Primary	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	Cmax = maximum observed plasma concentration	Day -7 and Week 15
Secondary	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	AUC-last = area under the plasma concentration curve from time 0 to the last quantifiable observation	Day -7 and Day 8
Secondary	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	Cmax = maximum observed plasma concentration	Day -7 and Day 8
Secondary	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	AUC-inf = area under the plasma concentration curve from time 0 to infinity	Day -7 and Day 8
Secondary	Number of adverse events		From Day 1 up to Week 30
Secondary	Presence of anti-drug antibodies (yes/no)		From Day 1 up to Week 30