Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day and single oral dose of Sumatriptan 25 mg tablet on Day 8 in Part 2 under fed conditions.

Participants received single oral dose of digoxin tablet (0.25 mg) on Day 1 and Day 10 in Part 1 under fed conditions.

Participants received single oral dose of metformin 10 mg solution on Day 1 and Day 10 in Part 1 under fed conditions.

Participants received single oral dose of rosuvastatin tablet (10 mg) on Day 1 and Day 10 in Part 1 under fed conditions.

Participants received single dose of sumatriptan tablet (25 mg) on Day 1 and Day 8 in Part 2 under fed conditions.

The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

Cmax was obtained directly from the concentration versus time curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported.

Laboratory investigation included hematology, biochemistry and urinalysis. Clinical meaningful changes were determined by the investigator. The number of participants with clinically relevant changes from baseline in laboratory parameters were reported.

Vital signs included body temperature, systolic and diastolic blood pressure and pulse rate. Clinical relevance was determined by the investigator. The number of participants with clinically relevant changes from baseline in vital signs were reported.

12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical relevance was determined by the investigator. The number of participants with clinically relevant changes from baseline in 12-Lead ECG findings were reported.

Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

Tmax was the time to reach the maximum observed concentration collected during a dosing interval. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin.

As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin.

As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

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 was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

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 was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

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 was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

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 was calculated using the mixed log-linear trapezoidal rule (linear up, log down). As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was 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; Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

Ae0-36 was calculated as the cumulative amount excreted from time zero (= dosing time) to the end of the collection interval after dosing, for metformin only. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

CLr was calculated as Ae0-36 divided by AUC0-36, for metformin only. AUC0-36: AUC from time zero (= dosing time) to 36 hours post-dose (metformin only) calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

Total of all reporting groups

The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Cmax was obtained directly from the concentration versus time curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

An adverse event (AE) was 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. Serious AE: 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. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.

The safety analysis set (SAF) included all participants, who were administered any dose of any study intervention.

Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported.

The SAF included all participants, who were administered any dose of any study intervention.

Laboratory investigation included hematology, biochemistry and urinalysis. Clinical meaningful changes were determined by the investigator. The number of participants with clinically relevant changes from baseline in laboratory parameters were reported.

The SAF included all participants, who were administered any dose of any study intervention.

Vital signs included body temperature, systolic and diastolic blood pressure and pulse rate. Clinical relevance was determined by the investigator. The number of participants with clinically relevant changes from baseline in vital signs were reported.

The SAF included all participants, who were administered any dose of any study intervention.

12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical relevance was determined by the investigator. The number of participants with clinically relevant changes from baseline in 12-Lead ECG findings were reported.

The SAF included all participants, who were administered any dose of any study intervention.

Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Tmax was the time to reach the maximum observed concentration collected during a dosing interval. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin.

As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin.

As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

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 was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

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 was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

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 was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

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 was calculated using the mixed log-linear trapezoidal rule (linear up, log down). As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was 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; Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was 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. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Ae0-36 was calculated as the cumulative amount excreted from time zero (= dosing time) to the end of the collection interval after dosing, for metformin only. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

CLr was calculated as Ae0-36 divided by AUC0-36, for metformin only. AUC0-36: AUC from time zero (= dosing time) to 36 hours post-dose (metformin only) calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.

PK population included all participants who have completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results, with adequate study intervention compliance.

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day on Days 4 to 12 in Part 1 under fed conditions.

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day and cocktail (digoxin 0.25 mg tablet, metformin 10 mg solution, rosuvastatin 10 mg tablet) on Day 10 in Part 1 under fed conditions.

Participants received single oral dose of Sumatriptan 25 mg tablet on Day 1 in Part 2 under fed conditions.

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day on Days 2 to 8 in Part 2 under fed conditions.

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day and single oral dose of Sumatriptan 25 mg tablet on Day 8 in Part 2 under fed conditions.