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Atopic DermatitisPhase 1NCT02647086

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

A Phase 1 study testing Dupilumab, Midazolam and Omeprazole in people with Atopic Dermatitis, run by Regeneron Pharmaceuticals at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atopic Dermatitis
What is being tested?
Dupilumab, Midazolam and Omeprazole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
5 sitesUnited States
Study dates
Dec 2015to Jul 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
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  • 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)
  • 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
  • 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
  • History or presence of alcohol or drug abuse within last 2 years
  • History of smoking within last 2 years
  • Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping
  • 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
  • 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
  • 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
  • History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening
  • 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.
  • 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
  • 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
  • Female patients who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study
  • Women who are using any form of hormonal contraceptives (eg, oral, injectables, implants, patches, rings, hormone-impregnated intrauterine devices [IUDs]) for birth control
  • Women unwilling to use adequate birth control, if of reproductive potential and sexually active.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Regeneron Study Site

    Berlin, New Jersey

  • Regeneron Study Site

    Centennial, Colorado

  • Regeneron Study Site

    Little Rock, Arkansas

  • Regeneron Study Site

    Minneapolis, Minnesota

  • Regeneron Study Site

    Raleigh, North Carolina

Other trials in United States

About this study

Official title: 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).

Keywords
Eczema
Medical subject headings
Dermatitis, Atopic, Eczema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DupilumabDrug

    Also called REGN668/SAR231893

  • MidazolamDrug

    Cytochrome P450 substrate

  • OmeprazoleDrug

    Cytochrome P450 substrate

  • WarfarinDrug

    Cytochrome P450 substrate

  • CaffeineDrug

    Cytochrome P450 substrate

  • MetoprololDrug

    Cytochrome P450 substrate

Study groups in NCT02647086
Study groupRoleWhat they receive
Period 1ExperimentalPatients will receive selected Cytochrome P450 substrates (Midazolam, Omeprazole, Warfarin, Caffeine, Metoprololin) in period 1 (day 1)
Receives: Drug: Midazolam; Drug: Omeprazole; Drug: Warfarin; Drug: Caffeine; Drug: Metoprolol
Period 2ExperimentalPatients 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).
Receives: Drug: Dupilumab; Drug: Midazolam; Drug: Omeprazole; Drug: Warfarin; Drug: Caffeine; Drug: Metoprolol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: At Baseline (day 1)

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

    Measured: At day 36

Secondary outcomes (1)

  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).

    Measured: Baseline up to day 134

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2016 (estimated)
  2. Study startDec 2015
  3. Primary completionJul 2016
  4. Study completionJul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02647086
Sponsor's protocol ID
R668-AD-1433
Status last verified
Aug 2016
First submitted
4 Jan 2016
Last updated
22 Aug 2016
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 29498038

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dupilumab, Midazolam and Omeprazole in people with Atopic Dermatitis, run by Regeneron Pharmaceuticals at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02647086, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2016.

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