Clinical trial NCT03934502: Effect of Meal Composition and Timing on Evobrutinib Bioavailability
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Evobrutinib
Pharmacokinetics
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2019-05-02
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
measure: Maximum Plasma Concentration Observed (Cmax) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
Secondary outcomes:
measure: Number of Participants With Treatment -Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Day 9
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings
timeFrame: Day 1 up to Day 9
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours After Drug Administration (AUC0-24) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
measure: Area Under The Concentration-Time Curve from Time Zero to Time 12 Hours (AUC0-12) of Evobrutinib
timeFrame: Pre-dose up to 12 Hours post-dose
measure: Time to Reach Maximum Concentration (Tmax) of Evobrutinib in Plasma
timeFrame: Pre-dose up to 24 hours post-dose
measure: Time Prior to the First Measurable (non-zero) Concentration of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
measure: Apparent Elimination Half Life (t1/2) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
measure: Apparent Clearance (CL/f) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
measure: Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: