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Effect of Meal Composition and Timing on Evobrutinib Bioavailability

Sponsor
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Completed
CT.gov ID
NCT03934502
Collaborator
(none)
20
Enrollment
1
Location
4
Arms
1.9
Actual Duration (Months)
10.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the Pharmacokinetics (PK) of the Phase II tablet formulation of Evobrutinib under fasted conditions, within 30 minutes after start of a light meal, one hour prior to start of a low-fat meal, and 2 hours after start of a low-fat meal.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Phase I, Open-Label, Randomized, Single-Dose, Four-Period, Four-Sequence Crossover Study to Compare the Effects of a Light Meal and of a Low-Fat Meal Timing on Evobrutinib Bioavailability in Healthy Volunteers
Actual Study Start Date :
Apr 15, 2019
Actual Primary Completion Date :
Jun 12, 2019
Actual Study Completion Date :
Jun 12, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Evobrutinib: Treatment Sequence A, B, C, D

Participant will receive single oral dose of evobrutinib after an overnight fast of at least 10 hours (Treatment A) for 3 days, followed by within 30 minutes after start of a light meal (Treatment B) for 2 days, followed by 1 hour prior to a low-fat meal (Treatment C) for 2 days, followed by 2 hours after start of low-fat meal (Treatment D) for 2 days. There will be 48 hours washout period between each treatment period.

Drug: Evobrutinib
Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A), within 30 minutes after start of a light meal (Treatment B), 1 hour prior to a low-fat meal (Treatment C), or 2 hours after start of a low-fat meal (Treatment D).
Other Names:
  • M2951

    		•
    Experimental: Evobrutinib: Treatment Sequence B, D, A, C

    Participant will receive single oral dose of evobrutinib within 30 minutes after start of a light meal (Treatment B) for 3 days, followed by 2 hours after start of a low-fat meal (Treatment D) for 2 days, followed by after an oversight fast of at least 10 hours (Treatment A) for 2 days, followed by 1 hour prior to a low-fat meal (Treatment C) for 2 days. There will be 48 hours washout period between each treatment period.

    Drug: Evobrutinib
    Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A), within 30 minutes after start of a light meal (Treatment B), 1 hour prior to a low-fat meal (Treatment C), or 2 hours after start of a low-fat meal (Treatment D).
    Other Names:
  • M2951

    		•
    Experimental: Evobrutinib: Treatment Sequence C, A, D, B

    Participant will receive single oral dose of evobrutinib 1 hour prior to a low-fat meal (Treatment C) for 3 days, followed by after an oversight fast of at least 10 hours (Treatment A) for 2 days, followed by 2 hours after start of a low-fat meal (Treatment D) for 2 days followed by within 30 minutes after start of a light meal (Treatment B) for 2 days. There will be 48 hours washout period between each treatment period.

    Drug: Evobrutinib
    Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A), within 30 minutes after start of a light meal (Treatment B), 1 hour prior to a low-fat meal (Treatment C), or 2 hours after start of a low-fat meal (Treatment D).
    Other Names:
  • M2951

    		•
    Experimental: Evobrutinib: Treatment Sequence D, C, B, A

    Participant will receive single oral dose of evobrutinib 2 hours after start of a low-fat meal (Treatment D) for 3 days, followed by 1 hour prior to a low-fat meal (Treatment C) for 2 days, followed by within 30 minutes after start of a light meal (Treatment B) for 2 days, followed by after an overnight fast of at least 10 hours (Treatment A) for 2 days. There will be 48 hours washout period between each treatment period.

    Drug: Evobrutinib
    Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A), within 30 minutes after start of a light meal (Treatment B), 1 hour prior to a low-fat meal (Treatment C), or 2 hours after start of a low-fat meal (Treatment D).
    Other Names:
  • M2951

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib [Pre-dose up to 24 hours post-dose]

    2. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of Evobrutinib [Pre-dose up to 24 hours post-dose]

    3. Maximum Plasma Concentration Observed (Cmax) of Evobrutinib [Pre-dose up to 24 hours post-dose]

    Secondary Outcome Measures

    1. Number of Participants With Treatment -Emergent Adverse Events (TEAEs) [Day 1 up to Day 9]

    2. Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings [Day 1 up to Day 9]

      Number of participants with clinically significant change from baseline in vital signs, laboratory parameters and electrocardiogram findings will be reported

    3. Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours After Drug Administration (AUC0-24) of Evobrutinib [Pre-dose up to 24 hours post-dose]

    4. Area Under The Concentration-Time Curve from Time Zero to Time 12 Hours (AUC0-12) of Evobrutinib [Pre-dose up to 12 Hours post-dose]

    5. Time to Reach Maximum Concentration (Tmax) of Evobrutinib in Plasma [Pre-dose up to 24 hours post-dose]

    6. Time Prior to the First Measurable (non-zero) Concentration of Evobrutinib [Pre-dose up to 24 hours post-dose]

    7. Apparent Elimination Half Life (t1/2) of Evobrutinib [Pre-dose up to 24 hours post-dose]

    8. Apparent Clearance (CL/f) of Evobrutinib [Pre-dose up to 24 hours post-dose]

    9. Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib [Pre-dose up to 24 hours post-dose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Participants are overtly healthy as medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring

    • Participants are stable non-smokers for at least 3 months preceding screening

    • Male or female participants agree to be consistent with local regulations on contraception methods

    • Female participants are not pregnant or breastfeeding, and at least one of the following condition applies:

    • Not a woman of childbearing potential (WOCBP) or

    • If a WOCBP, use a highly effective contraceptive method (that is, with a failure rate of less than (<) 1 percent per year, preferably with low user dependency for the following time period:

    • Before the first dose of the study intervention, if using hormonal contraception:

    • Has completed at least one 4-week cycle of an oral contraception pill and either had or has begun her menses or

    • Has used a depot contraceptive or extended-cycle oral contraceptive for least 28 days and has a documented negative pregnancy test using a highly sensitive assay and

    • A barrier method

    • During the intervention period

    • After the study intervention period (that is after the last dose of study intervention is administered) for at least 90 days, plus 30 days (a menstrual cycle) after the last dose of study intervention and agree not to donate eggs (ova, oocytes) for reproduction during this period. The Investigator evaluates the effectiveness of the contraceptive method in relationship to the first dose of study intervention

    • Females have a negative serum pregnancy test at the Screening Visit and within 24 hours before the first dose of study intervention If a urine test cannot be confirmed as negative (example: an ambiguous result), a serum pregnancy test is required

    • The Investigator reviews the medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female with an early undetected pregnancy

    • Male participants should agree to the following during the study intervention period and for at least 3 months

    • after the last dose of study intervention:

    • Refrain from donating sperm,

    • plus either:

    • Abstain from intercourse with a female, Or

    • use a male condom:

    • When having sexual intercourse with a WOCBP, who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of <1 percent per year, since a condom may break or leak

    • Other protocol defined inclusion criteria could apply

    Exclusion Criteria:

    • History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.

    • Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to screening

    • History of any malignancy

    • History of chronic or recurrent acute infection or any bacterial, viral, parasitic or fungal infections within 30 days prior to screening and at any time between screening and admission, or hospitalization due to infection within 6 months prior to screening

    • History of shingles within 12 months prior to screening

    • History of drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients

    • History of alcoholism or drug abuse within 2 years prior to screening, or evidence of such abuse as indicated by the laboratory assays conducted during screening

    • History of residential exposure to tuberculosis, or a positive QuantiFERON® test within 4 weeks prior to screening

    • Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to screening

    • Any condition, including findings in the laboratory tests, medical history, or other screening assessments, that in the opinion of the Investigator constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study's objectives, conduct, or evaluation

    • Other protocol defined exclusion criteria could apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Nuvisan GmbH Neu-Ulm Germany 89231

    Sponsors and Collaborators

    • Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

    Investigators

    • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
    ClinicalTrials.gov Identifier:
    NCT03934502
    Other Study ID Numbers:
    • MS200527_0072
    • 2019-000877-21
    • NCT04200430
    First Posted:
    May 2, 2019
    Last Update Posted:
    Jul 7, 2020
    Last Verified:
    Jul 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
    Evobrutinib
    Pharmacokinetics

    Study Results

    No Results Posted as of Jul 7, 2020