NCT03556592|CompletedPhase 1FDA Drug

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

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

LEO Pharma ClinicalTrials.gov

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2 other identifiers

LP0162-13422018-000534-35

Study Type

interventional

Target

Locations

3 countries

Sites

Timeline

RegisteredJun 2018

StartedAug 2018

CompletionJun 2020

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

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_1

Timeline

Completed

Started Aug 2018

Geographic Reach

3 countries

12 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.9 years study duration

First Submitted

Initial submission to the registry

May 30, 2018

Completed

15 days until next milestone

First Posted

Study publicly available on registry

June 14, 2018

Completed

2 months until next milestone

Study Start

First participant enrolled

August 13, 2018

Completed

1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 16, 2020

Completed

3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 20, 2020

Completed

Last Updated

February 24, 2025

Status Verified

October 1, 2020

Enrollment Period

1.6 years

First QC Date

May 30, 2018

Last Update Submit

February 21, 2025

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (2)

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
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 Outcomes (5)

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
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
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
Number of adverse events
From Day 1 up to Week 30
Presence of anti-drug antibodies (yes/no)
From Day 1 up to Week 30

Study Arms (1)

All subjects

EXPERIMENTAL

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: TralokinumabDrug: CaffeineDrug: WarfarinDrug: OmeprazoleDrug: MetoprololDrug: Midazolam Hydrochloride

Interventions

TralokinumabDRUG

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.

All subjects

CaffeineDRUG

1x 100 mg tablet

All subjects

WarfarinDRUG

2x 5 mg tablets

All subjects

OmeprazoleDRUG

1x 20 mg capsule

All subjects

MetoprololDRUG

1x 100 mg tablet

All subjects

Midazolam HydrochlorideDRUG

1 mL of 2 mg/mL oral solution/syrup

All subjects

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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):
+7 more criteria

Contact the study team to confirm eligibility.