Open Label, Drug-Drug Interaction (DDI) Study of Dupilumab (REGN668/SAR231893) in Patients With Moderate to Severe Atopic Dermatitis (AD)

August 18, 2016 updated by: Regeneron Pharmaceuticals

An Open-Label, Drug-Drug Interaction Study to Examine the Effects of Dupilumab on the Pharmacokinetics of Selected Cytochrome P450 Substrates in Adult Patients With Moderate to Severe Atopic Dermatitis

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States
        • Regeneron Study Site
    • Colorado
      • Centennial, Colorado, United States
        • Regeneron Study Site
    • Minnesota
      • Minneapolis, Minnesota, United States
        • Regeneron Study Site
    • New Jersey
      • Berlin, New Jersey, United States
        • Regeneron Study Site
    • North Carolina
      • Raleigh, North Carolina, United States
        • Regeneron Study Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patient, aged 18 years or older
  2. Diagnosis of Chronic AD, defined as diagnosis of AD for at least 3 years before the screening visit
  3. Eczema Area Severity Index (EASI) score ≥16 at the screening and baseline visits
  4. Investigator's Global Assessment (IGA) score ≥3 (on the 0 to 4 IGA scale) at the screening and baseline visits
  5. ≥10% Body Surface Area (BSA) of AD involvement at the screening and baseline visits
  6. 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)
  7. Provide signed informed consent

Exclusion Criteria:

  1. Prior participation in a dupilumab clinical trial

  2. The use of any of the following treatments within 4 weeks before the baseline visit:

    • Systemic corticosteroids
    • Immunosuppressive/immunomodulating drugs
    • Phototherapy for AD
  3. 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.

  4. Any contraindication to one or more of the following drugs, according to the applicable labeling:

    • Midazolam
    • Omeprazole
    • Warfarin
    • Caffeine
    • Metoprolol

  5. 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)
    • Charbroiled meats
    • Caffeinated beverages, foods or drugs containing caffeine Patients who are not willing to abstain from the consumption of these food items and/or beverages for certain periods during the study will also be excluded
  6. History of excessive consumption of beverages containing caffeine (more than 4 cups or glasses per day). Patients who are not willing to abstain from the consumption of caffeine during certain periods of the study will also be excluded
  7. History or presence of alcohol or drug abuse within last 2 years
  8. History of smoking within last 2 years
  9. Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping

  10. Presence of any one or more of the following lab abnormalities at screening:

    • Platelet count ≤100 x 10^3/µL
    • Neutrophils ≤1 x 10^3/µL
    • Creatinine phosphokinase (CPK) >10 x upper limit of normal (ULN)
    • International normalized ratio (INR) ≥2
  11. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit, or superficial skin infections within 1 week before the screening visit
  12. Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune compromised status, as judged by the investigator
  13. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening
  14. Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (Hep C Ab) at the screening visit. NOTE: Patients who are HBsAg negative and HBsAb positive are considered immune after a natural infection has cleared or they have been vaccinated against hepatitis B. Therefore, they are acceptable for the study.
  15. History of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix, and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin
  16. History of clinical endoparasitosis (ie, helminth infection) within 12 months before the baseline visit, or high risk of helminth infection, such as residence within or recent travel (within 12 months before the baseline visit) to areas endemic for endoparasitoses, where the circumstances are consistent with parasite exposure (eg, extended stay, rural or slum areas, lack of running water, consumption of uncooked, undercooked, or otherwise potentially contaminated food, close contact with carriers and vectors, etc), unless subsequent medical assessments (eg, stool exam, blood tests, etc) have ruled out the possibility of parasite infection/infestation
  17. Female patients who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study
  18. Women who are using any form of hormonal contraceptives (eg, oral, injectables, implants, patches, rings, hormone-impregnated intrauterine devices [IUDs]) for birth control
  19. Women unwilling to use adequate birth control, if of reproductive potential and sexually active.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Period 1
Patients will receive selected Cytochrome P450 substrates (Midazolam, Omeprazole, Warfarin, Caffeine, Metoprololin) in period 1 (day 1)
Drug: Midazolam
Cytochrome P450 substrate
Drug: Omeprazole
Cytochrome P450 substrate
Drug: Warfarin
Cytochrome P450 substrate
Drug: Caffeine
Cytochrome P450 substrate
Drug: Metoprolol
Cytochrome P450 substrate
Experimental: Period 2
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: Dupilumab
Other Names:
  • REGN668/SAR231893
Drug: Midazolam
Cytochrome P450 substrate
Drug: Omeprazole
Cytochrome P450 substrate
Drug: Warfarin
Cytochrome P450 substrate
Drug: Caffeine
Cytochrome P450 substrate
Drug: Metoprolol
Cytochrome P450 substrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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)
Time Frame: At Baseline (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)
Time Frame: At day 36
At day 36

Secondary Outcome Measures

Outcome Measure
Time Frame
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).
Time Frame: Baseline up to day 134
Baseline up to day 134

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regeneron Pharmaceuticals

Collaborators

Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

January 4, 2016

First Submitted That Met QC Criteria

January 4, 2016

First Posted (Estimate)

January 6, 2016

Study Record Updates

Last Update Posted (Estimate)

August 22, 2016

Last Update Submitted That Met QC Criteria

August 18, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R668-AD-1433

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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