Relative Bioavailability of Evobrutinib Tablet Batches

A Phase I, Open-Label Study of the Relative Bioavailability of Evobrutinib Tablet Manufacturing Batches in Healthy Participants

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07214922

Enrollment

Registered

2025-10-09

Start date

2023-01-18

Completion date

2023-02-24

Last updated

2025-12-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Evobrutinib, Pharmacokinetics, Relative Bioavailability, Crossover

Brief summary

The main purpose of the study is to compare the Pharmacokinetics (PK), safety and tolerability of different manufacturing batches of M2951 tablet formulation relative to a reference batch under fasted conditions in healthy participants.

Interventions

DRUGTreatment A

Participants will receive single dose of Treatment A in treatment period 1, 2, 3 or 4 under fasted conditions.

DRUGTreatment B

Participants will receive single dose of Treatment B in treatment period 1, 2, 3 or 4 under fasted conditions.

DRUGTreatment C

Participants will receive single dose of Treatment C in treatment period 1, 2, 3 or 4 under fasted conditions.

DRUGTreatment D

Participants will receive single dose of Treatment D in treatment period 1, 2, 3 or 4 under fasted conditions.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* Participants who are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection, or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion * Participants who have a body weight within 50.0 and 100.0 kilogram (kg) (inclusive) and Body Mass Index within the range 19.0 and 30.0 kg/ meter square (m2) (inclusive) * Female participant who agrees to use appropriate contraception and barrier methods. * Male participants: No contraception needed * Participants who are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and this protocol * Participants who are stable non-smokers for at least 3 months preceding Screening * Other protocol defined inclusion criteria could apply

Exclusion criteria

* Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, musculoskeletal, genitourinary, immunological, dermatological, connective tissue, psychiatric (due to rare risk of hallucinations, agitation and activation of psychosis), and other diseases or disorders, and epilepsy, as determined by medical evaluation * Participants with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease will be excluded from the study * Participants with prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to the first administration of study intervention * Participants with history of any malignancy * Participants with history of seizures * Participants with history of pharmacologically treated psychiatric disease * Participants with 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 the first administration of study intervention * Participants with history of shingles within 12 months prior to Screening * Participants with history of drug hypersensitivity * Participants with history of residential exposure to tuberculosis, or a positive QuantiFERON® test within 4 weeks prior to or at the time of Screening * Participants positive for 1. hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or Human Immunodeficiency Virus (HIV) I and II tests at Screening 2. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening and Day -1 * Participants with any condition, including findings in the laboratory tests, medical history (example heart failure, hypokalemia, family history of Long QT Syndrome), 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 * Participants with history of administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Day 1. * Participants with history of administration of other types of vaccines is allowed until 14 days before the first administration of study intervention, thereafter it is prohibited until the end of the study. * Participants with Moderate or strong inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4)/5 or Pgp within 4 weeks prior to the first administration of study intervention * Participants with use of any prescribed medicine or over-the-counter drug or dietary supplement, including herbal remedies, vitamins, and minerals, antacids and dietary supplements such as fish oils within 2 weeks or 5 times the half-life of the respective drug, whichever is longer, prior to the first administration of study intervention * Participants with use of any investigational drug in any clinical study within 60 days prior to Day 1 administration, or have used an experimental monoclonal antibody within the past 1 year prior to Day 1, or have participated in a study evaluating a Bruton Tyrosine Kinase (BTK) inhibitor within 60 days, or are on extended follow-up in a clinical study, even if last administration of a study intervention was more than 60 days ago, or 5 half-lives of the investigational drug, whichever is longer, prior to the first administration of study intervention * Participants with a medical history and physical examination results that include any ongoing clinically relevant findings as judged by the Investigator * Participants with clinically relevant findings (excluding minor, not clinically relevant excursions from normal ranges, as judged by the Investigator) at Screening in biochemistry, hematology, coagulation, and urinalysis examinations for the age of the participant, as judged by the Investigator: * Alanine aminotransferase, aspartate aminotransferase: above upper limit of normal (ULN) * Creatinine: above normal limits * Absolute lymphocyte count, absolute neutrophil count: below limit of reference range. * Amylase and lipase above normal ranges; minor deviations are allowed, if not clinically relevant. * Participants with estimated glomerular rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation (2009) \< 90 milliliters/minute(mL/min) at Screening. In case of a borderline result between ≥ 80 and \< 90 mL/min, Cystatin C will be determined in addition, and the participant will only be included if the Cystatin C value is below the upper limit of normal * Participants with semi-supine systolic blood pressure \> 140 mmHg or \< 90 millimeters of mercury (mmHg), diastolic blood pressure \> 90 mmHg or \< 50 mmHg, and pulse rate \> 90 or \< 50 beats per minute (bpm) at Screening. * Participants with consumption of alcohol from 48 hours prior to first administration of study intervention. * Other protocol defined

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7	AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7	Cmax was obtained directly from the concentration versus time curve.

Secondary

Measure	Time frame	Description
Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure	Baseline (Pre-dose), 2 hours post-dose	Diastolic blood pressure and systolic blood pressure were measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Change From Baseline in Vital Signs: Temperature	Baseline (Pre-dose), 2 hours post-dose	Temperature was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Change From Baseline in Vital Signs: Pulse Rate	Baseline (Pre-dose), 2 hours post-dose	Pulse rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Change From Baseline in Vital Signs: Respiratory Rate	Baseline (Pre-dose), 2 hours post-dose	Respiratory rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate	Baseline (Pre-dose), 2 hours post-dose	Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions
Change From Baseline in Electrocardiograms (ECGs) Parameter: RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration	Baseline (Pre-dose), 2 hours post-dose	RR Duration, QT Duration, QTcF Duration, PR Duration, QRS Duration was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions.
Number of Participants With Treatment- Emergent Adverse Events (TEAEs)	Up to 34 days	An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs.
Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7	The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Evobrutinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7	Time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Terminal Half Life (T1/2) of Evobrutinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7	Terminal half-life was calculated as log2 divided by lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Apparent Total Body Clearance (CL/f) of Evobrutinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7	Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for Evobrutinib.
Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7	Vz/f is defined as the apparent volume of distribution during the terminal phase following extravascular administration for Evobrutinib.
Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero Extrapolated to Infinity [Frel(AUC0-inf)] of Evobrutinib (Treatment B, C and D) Compared to Evobrutinib Reference Treatment A	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7	Relative Bioavailability in percentage of each treatment (B, C, and D) in relation to the reference Treatment (A) was calculated as Frel = 100 multiplied by (AUC0-inf \[treatment B, C, D\]) multiplied by Dose \[treatment A\] divided by (AUC0-inf \[treatment A\]) multiplied by Dose \[treatment B, C, D\]. Treatment A to determine relative bioavailability.
Number of Participants With Clinically Significant Changes in Laboratory Parameters	Screening up to Day 8	Laboratory investigation included hematology, biochemistry and urinalysis. The number of participants with clinically significant changes from baseline in laboratory parameters were reported. Clinical significance was determined by the investigator.
Number of Participants With Treatment- Emergent Adverse Events (TEAEs) by Severity	Up to 34 days	The Investigator assessed the severity of each AE and SAE reported during the study and assign it to one of the following categories: Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities; Severe: An event that prevents normal everyday activities. Do not confuse an AE that is assessed as severe with a SAE. Severe is a category used to rate the intensity of an event; both AEs and SAEs can be assessed as severe.

Countries

Germany

Participant flow

Participants by arm

Arm	Count
Sequence 1: Treatment A-B-C-D Participants received single oral dose of reference treatment (treatment A) of Evobrutinib (45 milligrams \[mg\]) on Day 1 in period 1, followed by single oral dose of lower dissolution bound batch (treatment B) of Evobrutinib (45 mg) on Day 3 in period 2, followed by single oral dose of upper dissolution bound batch (treatment C) of Evobrutinib (45 mg) on Day 5 in period 3 and followed by single oral dose of hammer milled batch (treatment D) of Evobrutinib (45 mg) on Day 7 under fasted condition in period 4. A washout period of 48 hours was maintained between 4 treatment periods.	7
Sequence 2: Treatment B-D-A-C Participants received single oral dose of lower dissolution bound batch (treatment B) of Evobrutinib (45 mg) on Day 1 in period 1, followed by single oral dose of hammer milled batch (treatment D) of Evobrutinib (45 mg) on Day 3 in period 2, followed by single oral dose of reference treatment (treatment A) of Evobrutinib (45 (mg) on Day 5 in period 3 and followed by single oral dose of upper dissolution bound batch (treatment C) of Evobrutinib (45 mg) on Day 7 under fasted condition in period 4. A washout period of 48 hours was maintained between 4 treatment periods.	7
Sequence 3: Treatment C-A-D-B Participants received single oral dose of upper dissolution bound batch (treatment C) of Evobrutinib (45 mg) on Day 1 in period 1, followed by single oral dose of reference treatment (treatment A) of Evobrutinib (45 (mg) on Day 3 in period 2, followed by single oral dose of hammer milled batch (treatment D) of Evobrutinib (45 mg) on Day 5 in period 3 and followed by single oral dose of lower dissolution bound batch (treatment B) of Evobrutinib (45 mg) on Day 7 under fasted condition in period 4. A washout period of 48 hours was maintained between 4 treatment periods.	7
Sequence 4: Treatment D-C-B-A Participants received single oral dose of hammer milled batch (treatment D) of Evobrutinib (45 mg) on Day 1 in period 1, followed by single oral dose of upper dissolution bound batch (treatment C) of Evobrutinib (45 mg) on Day 3 in period 2, followed by single oral dose of lower dissolution bound batch (treatment B) of Evobrutinib (45 mg) on Day 5 in period 3 and followed by single oral dose of reference treatment (treatment A) of Evobrutinib (45 (mg) on Day 7 under fasted condition in period 4. A washout period of 48 hours was maintained between 4 treatment periods.	7
Total	28

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	0	1	0
Overall Study	DROPPED OUT ON DAY 5; PRIVATE REASONS	0	1	0	0

Baseline characteristics

Characteristic	Total	Sequence 1: Treatment A-B-C-D	Sequence 2: Treatment B-D-A-C	Sequence 3: Treatment C-A-D-B	Sequence 4: Treatment D-C-B-A
Age, Continuous	35 Years STANDARD_DEVIATION 9.9	30 Years STANDARD_DEVIATION 5.6	37 Years STANDARD_DEVIATION 10.1	37 Years STANDARD_DEVIATION 12.8	35 Years STANDARD_DEVIATION 10.4
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants	7 Participants	6 Participants	7 Participants	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	28 Participants	7 Participants	7 Participants	7 Participants	7 Participants
Sex: Female, Male Female	17 Participants	4 Participants	5 Participants	3 Participants	5 Participants
Sex: Female, Male Male	11 Participants	3 Participants	2 Participants	4 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 26	0 / 27	0 / 27	0 / 27
other Total, other adverse events	2 / 26	1 / 27	1 / 27	5 / 27
serious Total, serious adverse events	0 / 26	0 / 27	1 / 27	0 / 27

Outcome results

Primary

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

Population: Pharmacokinetic (PK) Analysis Set was a subset of the Safety Analysis Set and included all participants who receive at least one dose of active investigational medicinal product (IMP) and provide at least one measurable post-dose concentration.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib	198 hour×nanogram per milliliter (h×ng/mL)	Geometric Coefficient of Variation 44
Treatment B	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib	164 hour×nanogram per milliliter (h×ng/mL)	Geometric Coefficient of Variation 45.1
Treatment C	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib	207 hour×nanogram per milliliter (h×ng/mL)	Geometric Coefficient of Variation 44.6
Treatment D	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib	205 hour×nanogram per milliliter (h×ng/mL)	Geometric Coefficient of Variation 38.3

Primary

Maximum Observed Plasma Concentration (Cmax) of Evobrutinib

Cmax was obtained directly from the concentration versus time curve.

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	Maximum Observed Plasma Concentration (Cmax) of Evobrutinib	111 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 69.9
Treatment B	Maximum Observed Plasma Concentration (Cmax) of Evobrutinib	84.5 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 71.9
Treatment C	Maximum Observed Plasma Concentration (Cmax) of Evobrutinib	117 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 62.6
Treatment D	Maximum Observed Plasma Concentration (Cmax) of Evobrutinib	121 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 64.7

Secondary

Apparent Total Body Clearance (CL/f) of Evobrutinib

Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for Evobrutinib.

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	Apparent Total Body Clearance (CL/f) of Evobrutinib	227 Liter per hour	Geometric Coefficient of Variation 44
Treatment B	Apparent Total Body Clearance (CL/f) of Evobrutinib	275 Liter per hour	Geometric Coefficient of Variation 45.1
Treatment C	Apparent Total Body Clearance (CL/f) of Evobrutinib	217 Liter per hour	Geometric Coefficient of Variation 44.6
Treatment D	Apparent Total Body Clearance (CL/f) of Evobrutinib	219 Liter per hour	Geometric Coefficient of Variation 38.3

Secondary

Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib

Vz/f is defined as the apparent volume of distribution during the terminal phase following extravascular administration for Evobrutinib.

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib	627 Liters	Geometric Coefficient of Variation 84.1
Treatment B	Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib	843 Liters	Geometric Coefficient of Variation 111.4
Treatment C	Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib	658 Liters	Geometric Coefficient of Variation 89.2
Treatment D	Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib	522 Liters	Geometric Coefficient of Variation 74.2

Secondary

Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib

The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose on Days 1, 3, 5 and 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A	Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib	194 h×ng/mL	Geometric Coefficient of Variation 44.5
Treatment B	Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib	160 h×ng/mL	Geometric Coefficient of Variation 46.3
Treatment C	Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib	204 h×ng/mL	Geometric Coefficient of Variation 45.1
Treatment D	Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib	202 h×ng/mL	Geometric Coefficient of Variation 39.2

Secondary

Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate

Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions

Time frame: Baseline (Pre-dose), 2 hours post-dose