NCT02647086

Brief Summary

This is an open-label, single-sequence DDI study designed to examine the effects of dupilumab on the pharmacokinetics of selected cytochrome P450 substrates in adult patients with moderate to severe AD. The study consists of a screening period (day -35 to -2), study period 1 (day -1 to 7), study period 2 (day 8 to 50), and a follow-up period (day 51 to 135 \[end of study\]). Following completion of study period 2 (Day 50), patients will be given the option to enroll into the Open-Label Extension (OLE) study R668-AD-1225. Patients who decline will be followed for the next 12 weeks (Day 135).

Trial Health

87
On Track

Trial Health Score

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

Enrollment
14

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2015

Shorter than P25 for phase_1

Geographic Reach
1 country

5 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

Study Start

First participant enrolled

December 1, 2015

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

January 4, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 6, 2016

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2016

Completed
Last Updated

August 22, 2016

Status Verified

August 1, 2016

Enrollment Period

7 months

First QC Date

January 4, 2016

Last Update Submit

August 18, 2016

Conditions

Atopic Dermatitis

Keywords

Eczema

Outcome Measures

Primary Outcomes (2)

  • Ratio of Area Under Curve last (AUClast) and maximum concentration (Cmax) for Cytochrome P450 substrates from pre-dupilumab administration at baseline (period 1, day 1)

    At Baseline (day 1)

  • Ratio of AUClast and Cmax for CYP substrates 4 weeks after initiating a weekly regimen of dupilumab (period 2, day 36)

    At day 36

Secondary Outcomes (1)

  • Incidence of treatment-emergent adverse events (TEAEs) from day of first administration of dupilumab to end of study (day 50 for patients who enroll in the OLE study; day 134 for patients who decline participation in the OLE).

    Baseline up to day 134

Study Arms (2)

Period 1

EXPERIMENTAL

Patients will receive selected Cytochrome P450 substrates (Midazolam, Omeprazole, Warfarin, Caffeine, Metoprololin) in period 1 (day 1)

Drug: MidazolamDrug: OmeprazoleDrug: WarfarinDrug: CaffeineDrug: Metoprolol

Period 2

EXPERIMENTAL

Patients will receive dupilumab starting in Period 2 (day 8) and continue weekly through day 50; Patients will receive selected Cytochrome P450 substrates (Midazolam, Omeprazole, Warfarin, Caffeine, Metoprolol) in period 2 (at day 36).

Drug: DupilumabDrug: MidazolamDrug: OmeprazoleDrug: WarfarinDrug: CaffeineDrug: Metoprolol

Interventions

DupilumabDRUG
Also known as: REGN668/SAR231893
Period 2
MidazolamDRUG

Cytochrome P450 substrate

Period 1Period 2
OmeprazoleDRUG

Cytochrome P450 substrate

Period 1Period 2
WarfarinDRUG

Cytochrome P450 substrate

Period 1Period 2
CaffeineDRUG

Cytochrome P450 substrate

Period 1Period 2
MetoprololDRUG

Cytochrome P450 substrate

Period 1Period 2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female patient, aged 18 years or older
  • Diagnosis of Chronic AD, defined as diagnosis of AD for at least 3 years before the screening visit
  • Eczema Area Severity Index (EASI) score ≥16 at the screening and baseline visits
  • Investigator's Global Assessment (IGA) score ≥3 (on the 0 to 4 IGA scale) at the screening and baseline visits
  • ≥10% Body Surface Area (BSA) of AD involvement at the screening and baseline visits
  • Patients with documented recent history (within 6 months before the screening visit) of inadequate response to outpatient treatment with topical medications, or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks)
  • Provide signed informed consent

You may not qualify if:

  • Prior participation in a dupilumab clinical trial
  • The use of any of the following treatments within 4 weeks before the baseline visit:
  • Systemic corticosteroids
  • Immunosuppressive/immunomodulating drugs
  • Phototherapy for AD
  • Administration, within 14 days before baseline or within a period of 5 times the elimination half-life of the medication before baseline, whichever is longer, of any medication that is a known inducer or inhibitor of either one or more of the following CYP enzymes: CYP3A, CYP2C19, CYP2C9, CYD2D6, and CYP1A2. Patients who are on any of these medications at the time of screening and cannot be safely taken off these medications will be excluded from the study.
  • Any contraindication to one or more of the following drugs, according to the applicable labeling:
  • Midazolam
  • Omeprazole
  • Warfarin
  • Caffeine
  • Metoprolol
  • Consumption of any 1 or more of the following food items and/ or beverages within 1 week prior to baseline:
  • Grapefruit or grapefruit juice, apple or apple juice, orange or orange juice, lemons or lemon juice, limes or lime juice
  • Vegetables from the mustard green family (eg, broccoli)
  • +20 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Regeneron Study Site

Little Rock, Arkansas, United States

Location

Regeneron Study Site

Centennial, Colorado, United States

Location

Regeneron Study Site

Minneapolis, Minnesota, United States

Location

Regeneron Study Site

Berlin, New Jersey, United States

Location

Regeneron Study Site

Raleigh, North Carolina, United States

Location

Related Publications (1)

  • Davis JD, Bansal A, Hassman D, Akinlade B, Li M, Li Z, Swanson B, Hamilton JD, DiCioccio AT. Evaluation of Potential Disease-Mediated Drug-Drug Interaction in Patients With Moderate-to-Severe Atopic Dermatitis Receiving Dupilumab. Clin Pharmacol Ther. 2018 Dec;104(6):1146-1154. doi: 10.1002/cpt.1058. Epub 2018 Apr 2.

    PMID: 29498038DERIVED

MeSH Terms

Conditions

Dermatitis, AtopicEczema

Interventions

dupilumabMidazolamOmeprazoleWarfarinCaffeineMetoprolol

Condition Hierarchy (Ancestors)

Skin Diseases, GeneticGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesDermatitisSkin DiseasesSkin and Connective Tissue DiseasesSkin Diseases, EczematousHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Intervention Hierarchy (Ancestors)

BenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds2-PyridinylmethylsulfinylbenzimidazolesSulfoxidesSulfur CompoundsOrganic ChemicalsPyridinesHeterocyclic Compounds, 1-RingBenzimidazoles4-HydroxycoumarinsCoumarinsBenzopyransPyransXanthinesAlkaloidsPurinonesPurinesPhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsPropanolsAmines

Study Officials

  • Clinical Trial Management

    Regeneron Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 4, 2016

First Posted

January 6, 2016

Study Start

December 1, 2015

Primary Completion

July 1, 2016

Study Completion

July 1, 2016

Last Updated

August 22, 2016

Record last verified: 2016-08

Locations

US(5)