Trial record 2 of 38 for:    regeneron | Open Studies

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2015 by Regeneron Pharmaceuticals
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02647086
First received: January 4, 2016
Last updated: NA
Last verified: December 2015
History: No changes posted
  Purpose

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).


Condition Intervention Phase
Atopic Dermatitis
Drug: Dupilumab
Drug: Cytochrome P450 Substrates
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Regeneron Pharmaceuticals:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: December 2015
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Period 1
Patients will receive selected Cytochrome P450 substrates in period 1 (day 1)
Drug: Cytochrome P450 Substrates
  • Midazolam
  • Omeprazole
  • Warfarin
  • Caffeine
  • Metoprolol
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 in period 2 (at day 36).
Drug: Dupilumab
Other Name: REGN668/SAR231893
Drug: Cytochrome P450 Substrates
  • Midazolam
  • Omeprazole
  • Warfarin
  • Caffeine
  • Metoprolol

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02647086

Contacts
Contact: Clinical Trials Administrator clinicaltrials@regeneron.com

Locations
United States, Arkansas
Regeneron Study Site Recruiting
Little Rock, Arkansas, United States
United States, California
Regeneron Study Site Recruiting
La Mesa, California, United States
United States, Colorado
Regeneron Study Site Recruiting
Centennial, Colorado, United States
United States, Minnesota
Regeneron Study Site Recruiting
Minneapolis, Minnesota, United States
United States, New Jersey
Regeneron Study Site Recruiting
Berlin, New Jersey, United States
United States, North Carolina
Regeneron Study Site Recruiting
Raleigh, North Carolina, United States
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  More Information

No publications provided

Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02647086     History of Changes
Other Study ID Numbers: R668-AD-1433 
Study First Received: January 4, 2016
Last Updated: January 4, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Regeneron Pharmaceuticals:
Eczema

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Eczema
Genetic Diseases, Inborn
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Skin Diseases
Skin Diseases, Eczematous
Skin Diseases, Genetic

ClinicalTrials.gov processed this record on February 09, 2016